Original Article
Interleukin-1–Receptor Antagonist in Type 2 Diabetes Mellitus
N Engl J Med 2007; 356:1517-1526April 12, 2007
- Abstract
Background
The expression of interleukin-1–receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1β in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis.
Methods
In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1–receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic–euglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were changes in beta-cell function, insulin sensitivity, and inflammatory markers.
Results
At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drug-related serious adverse events.
Conclusions
The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation. (ClinicalTrials.gov number, NCT00303394.)
Media in This Article
Figure 1
Enrollment and Outcomes.Figure 2
Changes in Glycated Hemoglobin and Fasting Plasma Glucose Levels during the 13-Week Study Period.Article Activity
- Article
Type 2 diabetes mellitus occurs when beta-cell function fails to compensate for insulin resistance.1,2 Beta-cell function progressively deteriorates with an increasing duration of diabetes,3 partly because of beta-cell demise through apoptosis.4-6
Interleukin-1β, a proinflammatory cytokine7 implicated as an effector molecule of inflammatory beta-cell destruction leading to type 1 diabetes,8 inhibits the function and promotes the apoptosis of beta cells.9 Beta cells producing interleukin-1β have been observed in pancreatic sections obtained from patients with type 2 diabetes.10 Depending on culture conditions, high glucose levels increase beta-cell production and the release of interleukin-1β, followed by functional impairment and apoptosis.10-13 These findings suggest that intra-islet production of inflammatory mediators has a role in the pathogenesis of type 2 diabetes and that interleukin-1β is a potential therapeutic target for preserving beta-cell mass and function in patients with this condition.
Interleukin-1–receptor antagonist, a naturally occurring competitive inhibitor of interleukin-1 binding to the type I receptor,7,14 protects human beta cells from glucose-induced functional impairment and apoptosis.10 Interleukin-1–receptor antagonist is reported to have no agonistic activity.7,15 The expression of interleukin-1–receptor antagonist is decreased in beta cells obtained from patients with type 2 diabetes.16 Given these observations, we hypothesized that intervening in the islet balance between interleukin-1–receptor antagonist and interleukin-1β might improve beta-cell function and glycemic control in patients with type 2 diabetes.
Methods
Study Design
This placebo-controlled, double-blind, parallel-group study involved 70 patients with type 2 diabetes at two centers (31 patients in Denmark and 39 patients in Switzerland) who were recruited from January 2004 to March 2005. Patients received either once-daily recombinant human interleukin-1–receptor antagonist (100 mg of anakinra [Kineret] donated by Amgen) or placebo by subcutaneous self-administration in the morning for 13 weeks. Patients continued their baseline antidiabetic therapy, dietary habits, and other lifestyle habits.
The County Pharmacy of Zurich was responsible for the blinding and randomization procedure; the latter was performed with the use of permuted blocks within the recruiting center. The authors designed the study, gathered and analyzed the data, wrote the manuscript, and vouch for the accuracy and completeness of the data and the analysis. There was no confidentiality agreement between the authors or their institutions and Amgen, which provided the study drugs.
Patients
We conducted the study in accordance with the ethical guidelines of the Declaration of Helsinki II; the study design was approved by regional and institutional review boards. Written informed consent was obtained from all patients before randomization.
The inclusion criteria were an age of 20 years or more, type 2 diabetes diagnosed according to American Diabetes Association criteria17 with a duration of more than 3 months, a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of more than 27, and a glycated hemoglobin level of more than 7.5% (upper limit of the normal range, 6.4%). Eligible patients had had no changes in either types or doses of medications during the 3-month period preceding the study.
The exclusion criteria were the presence of autoantibodies to glutamic acid decarboxylase 65 or islet-cell autoantibody-2; a glycated hemoglobin level of more than 12%; a fasting C-peptide level of less than 400 pmol per liter; current treatment with antiinflammatory drugs, including corticosteroids and nonsteroidal antiinflammatory drugs (100 mg or less of aspirin per day was allowed); signs of current infection, including a C-reactive protein level of more than 30 mg per liter, fever, current treatment with antibiotics, chronic granulomatous infections (e.g., a previous diagnosis of tuberculosis or a current diagnosis based on chest radiography or a Mantoux test); a history of recurrent infection or a predisposition to infection; neutropenia (a leukocyte count of less than 2000 per cubic millimeter) or anemia (a hemoglobin level of less than 11 g per deciliter for men and less than 10 g per deciliter for women); pregnancy or breast-feeding (contraception for at least 3 months before inclusion was required for fertile women); liver or renal disease (a level of aspartate aminotransferase or alanine aminotransferase of more than three times the upper limit of the normal range and a serum creatinine level of more than 130 μmol per liter); ongoing or previous cancer; the use of any other investigational drug within 30 days before enrollment or within five half-lives of the medication used in the other study, whichever was the longer period; and immunosuppressive treatment or immunodeficiency.
Study Procedures
At baseline and 13 weeks, a 2-hour oral glucose-tolerance test was performed with 75 g of glucose, followed by measurements of plasma glucose, proinsulin, insulin, and C-peptide 10 minutes before and during the test and measurements of plasma glucose, insulin, and C-peptide 30, 60, 90, and 120 minutes after the test. Immediately after the end of the oral glucose-tolerance test, an intravenous injection of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine was administered. Blood was then sampled at 0, 3, 6, 9, and 12 minutes. The patients were asked to forgo their antidiabetic medication and to fast for 8 to 9 hours before the test.
At baseline and 13 weeks, euglycemic–hyperinsulinemic clamp studies18 and muscle biopsies were performed. All patients were asked to participate in the clamp and muscle-biopsy studies, although participation in these studies was not a requirement for remaining in the overall study. The patients were required to forgo antidiabetic treatment for 8 to 9 hours and to avoid strenuous physical exercise for 24 hours before the clamp study. The clamp procedure was performed 2 to 7 days after the oral glucose-tolerance test. Indirect calorimetry was performed during the insulin-stimulated 30-minute steady-state period. The insulin-sensitivity index during the clamp procedure was calculated by dividing the M value (the glucose infusion rate during the steady-state period divided by the total body weight) by the steady-state plasma insulin level.
Biopsy specimens were obtained from the vastus lateralis muscle immediately after the administration of the intravenous bolus at the end of the oral glucose-tolerance test. Messenger RNA (mRNA) from glucose transporter 4 (GLUT4) and peroxisome-proliferator–activated receptor γ coactivator 1α (PGC-1α)19,20 was quantified as described in the Supplementary Appendix (available with the full text of this article at www.nejm.org).
Levels of C peptide, insulin, and proinsulin were determined centrally at the Steno Diabetes Center. Insulin and proinsulin were assessed by enzyme-linked immunosorbent assays,21,22 and C-peptide levels were determined by a time-resolved fluoroimmunoassay.23 Measurements of glycated hemoglobin levels and routine clinical laboratory tests were performed in the central laboratory units of the two participating centers. For glycated hemoglobin, 22 coded samples from patients were tested at both laboratories. Regression analysis showed an r2 value of 0.97 for agreement between the test results (P<0.001). Serum adipokines were assayed with the use of Luminex technology (Millipore) according to the manufacturer's instructions.
A physical examination and blood tests were performed at baseline and at 4 and 13 weeks. Fasting plasma glucose levels were measured weekly at home by the patients. At baseline and 13 weeks, funduscopy was performed, and urinary albumin excretion, creatinine clearance, and (in women) human chorionic gonadotropin were measured.
Study End Points
The predefined primary end point was the change in the glycated hemoglobin level between baseline and 13 weeks. Predefined secondary end points included a change by week 13 in the area under the concentration–time curve (AUC) for stimulated C-peptide during an oral glucose-tolerance test and after intravenous stimulation, a change in the ratio of fasting proinsulin to insulin, a change in the insulin-sensitivity index derived from the oral glucose-tolerance test,24 a change in serum adipokine levels, a change in insulin sensitivity as assessed by a euglycemic–hyperinsulinemic clamp study (in the 35 patients who provided consent for this procedure), a change in insulin-regulated genes in biopsy specimens obtained from skeletal muscle, and changes in levels of fasting plasma glucose, interleukin-6, and C-reactive protein as markers of systemic inflammation.
Statistical Analysis
No interim analyses were carried out in this study. Data from all patients were analyzed. Values are expressed as means (±SD) unless otherwise specified. Differences were tested with the use of an unpaired t-test and with a Wilcoxon rank-sum test in the case of non-normal distribution. For categorical end points, Pearson's chi-square test was used. Correlations were performed by regression analysis. To analyze the effect of baseline characteristics on the primary end point, bivariate regression analyses including the treatment effect were performed. A P value of less than 0.05 was considered to indicate statistical significance. All reported P values are two-sided and have not been adjusted for multiple testing.
Results
Baseline Characteristics and Adherence
Seventy of the 124 subjects who underwent initial screening were randomly assigned to receive either anakinra or placebo (Figure 1Figure 1
Enrollment and Outcomes.). In the placebo group, a late positive Mantoux reaction developed in one patient, suggesting a reactivation of tuberculosis, and the patient was excluded before starting study medication. Table 1Table 1
Baseline Characteristics of the Patients. shows the baseline characteristics of the two study groups after randomization.All 34 patients receiving anakinra completed the study, as did 33 of 35 patients receiving placebo. In the placebo group, a phlegmonous foot infection developed in one patient after 4 weeks, and one patient identified his study-group assignment by performing a biochemical analysis of the study drug after 5 weeks. Two patients in the anakinra group and one in the placebo group reduced the dose of their antidiabetic medication during the intervention because of improvement in glycemia but were not excluded from the study, according to the intention-to-treat principle. The remaining patients did not change their antidiabetic therapy during the 13-week study period, as reflected by recorded types and doses of antidiabetic medication at baseline and at 4 and 13 weeks (data not shown). Thirty-five subjects (16 in the anakinra group and 19 in the placebo group) gave informed consent to participate in the clamp and muscle-biopsy studies. The patients who provided consent did not differ in their baseline characteristics from those who declined (data not shown). The peak serum levels of interleukin-1–receptor antagonist, measured 1 to 2 hours after the last injection of anakinra or placebo at 13 weeks, were 1256±958 μg per liter in the anakinra group and 0.6±0.4 μg per liter in the placebo group (P<0.001).
Primary End Point
The average absolute difference in glycated hemoglobin levels between baseline and 13 weeks was a reduction of 0.33 percentage point (from 8.69±0.17 to 8.37±0.21) in the anakinra group and an increase of 0.13 percentage point (from 8.23±0.28 to 8.37±0.46) in the placebo group, yielding a between-group difference of 0.46 percentage point (95% confidence interval [CI], 0.01 to 0.90; P=0.03) (Figure 2AFigure 2
Changes in Glycated Hemoglobin and Fasting Plasma Glucose Levels during the 13-Week Study Period.). The number of patients who had any reduction in glycated hemoglobin levels at 13 weeks was 21 of 34 patients in the anakinra group, as compared with 10 of 33 patients in the placebo group (P<0.001). Glycated hemoglobin levels were significantly lower in the anakinra group after 4 weeks than in the placebo group (an absolute reduction of 0.36%; 95% CI, 0.11 to 0.60; P=0.004) (Figure 2A). When the patients were stratified into three equal groups according to body-surface area as a surrogate for drug distribution volume, the difference in glycated hemoglobin levels in the anakinra group was a reduction of 0.84% in the lowest third (<2.00 m2), a reduction of 0.30% in the intermediate group (2.00 to 2.24 m2), and an increase of 0.11% in the highest third (>2.24 m2) (P=0.02 for all comparisons) (Figure 2C). Accordingly, body-surface area correlated with the changes in glycated hemoglobin levels in the anakinra group (r2=0.22, P=0.007) but not in the placebo group (r2=0.001, P=0.87).Secondary End Points
Glycemia
Fasting plasma glucose levels that were measured by the patients at home once weekly were consistently lower in the anakinra group than in the placebo group (Figure 2B). At 13 weeks, plasma glucose levels at the beginning and end of a 2-hour oral glucose-tolerance test were reduced by 0.6 mM (95% CI, 0.05 to 1.60; P=0.29) and 1.3 mM (95% CI, 0.00 to 2.6; P=0.05), respectively, in the anakinra group, as compared with the placebo group.
Beta-Cell Secretory Function
At 13 weeks, beta-cell function increased in the anakinra group and decreased in the placebo group (Figure 3Figure 3
Beta-Cell Secretory Function.). In particular, the ratio of proinsulin to insulin was markedly lower in the anakinra group (P=0.005). The changes in beta-cell function assessed on the basis of the AUC from the oral glucose-tolerance test and intravenous tests were significantly correlated (P<0.001) (data not shown). The change in beta-cell function was correlated with changes in glycated hemoglobin levels in patients in the anakinra group but not in the placebo group. The correlation between the change in glycated hemoglobin levels and the AUC for stimulated C-peptide during the oral glucose-tolerance test was r2=0.13 (P=0.04) in the anakinra group and r2=0.04 (P=0.76) in the placebo group; the correlation for intravenous stimulation was r2=0.32 (P<0.001) in the anakinra group and r2=0.03 (P=0.29) in the placebo group; and the correlation for the two tests combined was r2=0.18 (P=0.02) in the anakinra group and r2=0.01 (P=0.59) in the placebo group. Baseline glycated hemoglobin values did not correlate with the beta-cell secretion tests in patients in the anakinra group. The correlation between the starting glycated hemoglobin level and the AUC for stimulated C-peptide during the oral glucose-tolerance test was r2=0.05 (P=0.22), the correlation for intravenous stimulation was r2=0.09 (P=0.10), and the correlation for both tests combined was r2=0.06 (P=0.17).Insulin Sensitivity
With the dose of anakinra used in this study, no differences in insulin sensitivity were found at 13 weeks. The M value divided by the plasma insulin level during the steady-state period in the euglycemic–hyperinsulinemic clamp study was reduced by 0.13±1.76 μg of glucose per kilogram of body weight per picomole of insulin per minute in the anakinra group and by 0.56±2.52 μg of glucose per kilogram of body weight per picomole of insulin per minute in the placebo group (P=0.58). The insulin-sensitivity index, as calculated by the homeostasis model assessment (HOMA) on the basis of the oral glucose-tolerance test in all patients, increased by 0.003±0.179 square liter per milliunit of insulin per millimole of glucose in the anakinra group and by 0.029±0.228 square liter per milliunit of insulin per millimole of glucose in the placebo group (P=0.60). The insulin-sensitivity index on the basis of data from the oral glucose-tolerance test strongly correlated with the clamp data (r2=0.53, P<0.001). There was no correlation between insulin sensitivity as determined by the clamp method and the primary end point at 13 weeks (r2=0.005, P=0.60) and no change in oxidation rates of glucose, with an increase of 0.02±0.7 mg of oxidized glucose per kilogram per minute in the anakinra group and a decrease of 0.15±0.37 mg per kilogram per minute in the placebo group (P=0.44) or of fat, with a decrease of 0.05±0.26 mg per kilogram per minute in the anakinra group and an increase of 0.03±0.2 mg per kilogram per minute in the placebo group (P=0.36).
Markers of Systemic Inflammation
Levels of C-reactive protein were significantly lower after 4 and 13 weeks in the anakinra group than in the placebo group (P=0.02 after 4 weeks and P=0.002 after 13 weeks) (Figure 4AFigure 4
Markers of Systemic Inflammation.). Similar declines in interleukin-6 levels were observed (P<0.001 after both 4 and 13 weeks) (Figure 4B). Neither baseline values nor changes in levels of C-reactive protein or interleukin-6 were significantly correlated with changes in glycated hemoglobin in the anakinra group: r2<0.001 (P=0.89) for baseline C-reactive protein levels, r2<0.001 (P=0.95) for changes in C-reactive protein, r2=0.005 (P=0.70) for baseline interleukin-6, and r2=0.001 (P=0.86) for changes in interleukin-6. As previously observed,25 neutrophil and platelet counts were slightly and reversibly decreased during anakinra therapy. Neutrophil counts decreased by 1200±1400 per cubic millimeter in the anakinra group and by 100±1300 per cubic millimeter in the placebo group; platelet counts decreased by 16,000±25,400 per cubic millimeter in the anakinra group and increased by 3000±23,000 per cubic millimeter in the placebo group (P<0.001).Insulin-Regulated Gene Expression
Treatment with anakinra for 13 weeks did not significantly change the mRNA expression levels of the insulin-regulated genes GLUT4 (P=0.81) and PGC-1α (P=0.26) in biopsy specimens of skeletal muscle, with decreases of 0.23±1.43 for the relative expression levels of GLUT4 and 0.12±0.87 for PGC-1α normalized to the housekeeping gene cyclophilin A in the anakinra group, as compared with decreases of 0.34±0.72 in the expression levels of GLUT4 and 0.52±0.79 for PGC-1α in the placebo group.
Serum Adipokines
Levels of serum adipokines were not significantly changed at 13 weeks in either the anakinra group or the placebo group. The levels changed as follows for the comparison between the study groups: leptin, a decrease of 0.40±6.86 ng per milliliter in the anakinra group and an increase of 2.81±10.98 ng per milliliter in the placebo group (P=0.16); adiponectin, an increase of 3.69±11.36 μg per milliliter in the anakinra group and a decrease of 1.00±8.59 μg per milliliter in the placebo group (P=0.07); resistin, a decrease of 2.80±8.56 ng per milliliter in the anakinra group and an increase of 0.27±7.65 ng per milliliter in the placebo group (P=0.14); tumor necrosis factor α, a decrease of 0.13±1.44 pg per milliliter in the anakinra group and an increase of 0.11±1.56 pg per milliliter in the placebo group (P=0.52); monocyte chemotactic factor 1, an increase of 9.2±50.8 pg per milliliter in the anakinra group and a decrease of 3.3±93.0 pg per milliliter in the placebo group (P=0.50); and interleukin-8, a decrease of 0.81±4.55 pg per milliliter in the anakinra group and a decrease of 0.08±1.17 pg per milliliter in the placebo group (P=0.40).
Other Outcomes
The baseline body weight and BMI were significantly correlated with changes in glycated hemoglobin levels (covariate effect, P=0.003 and P=0.004, respectively; treatment effect, P=0.08 and P=0.05, respectively; and combined effect, P=0.001 and P=0.002, respectively). This correlation was not observed for the other baseline variables.
Adverse Events
There were no significant changes in BMI in either group from baseline to 13 weeks, with levels changing from 31.5±5.2 to 31.8±5.6 in the anakinra group (P=0.82) and 31.8±4.4 to 32.0±4.4 in the placebo group (P=0.85) (P=0.38 for the comparison between study groups). No patient withdrew from the study because of drug-related adverse events. In particular, symptomatic hypoglycemia was not observed, even in patients with a marked improvement in glycated hemoglobin levels. All reported adverse events are listed in Table 2Table 2
Adverse Events.. In the anakinra group, the improvement in glycated hemoglobin levels did not differ between patients who had injection-site reactions and those who did not. There was a decrease of 0.24±0.18% in the glycated hemoglobin level in patients with injection-site reactions and a decrease of 0.64±0.32% in those without injection-site reactions (P=0.54). No changes were observed in blood pressure or heart rate or in levels of serum sodium, potassium, aspartate aminotransferase, alanine aminotransferase, lipids (including free fatty acids, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides), cystatin C, or creatinine or in creatinine clearance, 24-hour urinary albumin excretion, or retinal fundus. Total hemoglobin was unchanged, a finding that made changes in erythrocyte turnover unlikely as a confounder.Discussion
Our study shows that antagonism of interleukin-1 signaling with anakinra improved glycemic control in patients with type 2 diabetes, most likely through enhanced beta-cell secretory function. Indeed, improved glycemia in patients who received anakinra correlated with improved measures of beta-cell secretory capacity. There were no alterations in insulin sensitivity on the basis of insulin clamp studies, insulin sensitivity indexes modeled on the oral glucose-tolerance test, insulin-regulated gene expression in skeletal muscle, or serum adipokine levels. Finally, the BMIs of patients remained stable, thus excluding an anorexigenic effect of anakinra. However, we cannot exclude the possibility that higher doses of anakinra might improve insulin sensitivity.
Neither baseline levels of C-reactive protein or interleukin-6 nor changes in the levels correlated with changes in glycated hemoglobin levels, suggesting that reduced systemic inflammation did not play an important part in improved insulin secretion. Genetic ablation of systemic interleukin-1 action causes obesity.26,27 It has therefore been proposed that interleukin-1 regulates body composition and fat distribution, mainly through the regulation of feeding behavior, satiety regulation, and energy metabolism, including thermogenesis. The integral physiological measure of these actions is body weight. In our study, the inhibition of the action of interleukin-1 by anakinra did not increase body weight.
Limitations of our study include its short duration and the lack of dose finding. Considering the short half-life of anakinra (6 to 8 hours), it is possible that higher doses or longer-lasting antagonism of interleukin-1 might improve the outcome.28 The association between body weight or body-surface area at baseline and the glycemic outcome suggests that the anakinra dose might be increased according to the drug-distribution volume.
Apart from self-limited local reactions at the injection site, we observed no clear difference in the frequency of adverse events between the anakinra group and the placebo group. No patient stopped treatment because of adverse reactions. Symptomatic hypoglycemia was not reported by any patient. A potential concern with the use of interleukin-1 blockade is the inhibition of innate immunity and the occurrence of infection. However, in more than 100,000 patients with rheumatoid arthritis who underwent long-term treatment with anakinra, there was no significant increase in the incidence of infectious disease, despite concomitant immunosuppression.28
In summary, our study suggests that antagonism of interleukin-1 has possible therapeutic potential in the treatment of type 2 diabetes. Further studies are needed to test higher doses of anakinra, to evaluate its long-term use, and to test interleukin-1 antagonists that have a prolonged half-life, with the aim of preventing beta-cell destruction and promoting beta-cell regeneration in type 2 diabetes.
Supported by the Bonizzi-Theler and Hartmann-Müller Foundations, the Center of Clinical Studies at the University of Zurich, the Swiss National Science Foundation, the European Union, and Novo Nordisk. Amgen provided the study drugs at no cost.
Dr. Donath is listed as the inventor on a patent (WO6709) filed in 2003 for the use of an interleukin-1–receptor antagonist for the treatment of or prophylaxis against type 2 diabetes. The patent is owned by the University of Zurich, and Dr. Donath has no financial interest in the patent. Dr. Vølund reports being an employee of Novo Nordisk. Drs. Larsen, Vaag, Vølund, and Mandrup-Poulsen report having an equity interest in Novo Nordisk. Drs. Vaag and Mandrup-Poulsen report receiving grant support from Novo Nordisk. No other potential conflict of interest relevant to this article was reported.
Drs. Larsen, Faulenbach, Mandrup-Poulsen, and Donath contributed equally to this article.
We thank Erol Cerasi and Steven Kahn for their advice and critical reading of the manuscript; study nurses Erika Wettstein and Regula Messmer; laboratory technicians Hanne Foght, Helle Niebling, Charlotte Leth, Marianne Modest, and Margaretha Siegfried-Kellenberger; and study administrators Karen Kruse and Michèle Rothfuchs.
Source Information
From the Steno Diabetes Center, Gentofte (C.M.L., A. Vaag, T.M.-P.), and Biostatistics, Novo Nordisk, Bagsvaerd (A. Vølund) — both in Denmark; the Clinic for Endocrinology and Diabetes, University Hospital Zurich and Center for Integrative Human Physiology (M.F., J.A.E., M.Y.D.), and the Department of Biostatistics, University of Zurich (B.S.) — both in Zurich; and the University of Lund, Lund (A. Vaag), and the Karolinska Institute, Stockholm (T.M.-P.) — both in Sweden.
Address reprint requests to Dr. Donath at the Division of Endocrinology and Diabetes, University Hospital, CH-8091 Zurich, Switzerland, or at marc.donath@usz.ch.
- References
References
1
Cerasi E ,Luft R . Insulin response to glucose infusion in diabetic and non-diabetic monozygotic twin pairs: genetic control of insulin response? Acta Endocrinol (Copenh) 1967;55:330-345
Medline2
DeFronzo RA . Lilly Lecture 1987. The triumvirate: beta-cell, muscle, liver -- a collusion responsible for NIDDM. Diabetes 1988;37:667-687
Web of Science | Medline3
U.K. Prospective Diabetes Study Group. U.K. Prospective Diabetes Study 16 -- overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 1995;44:1249-1258[Erratum, Diabetes 1996;45:1655.]
CrossRef | Web of Science | Medline4
Butler AE ,Janson J ,Bonner-Weir S ,Ritzel R ,Rizza RA ,Butler PC . Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102-110
CrossRef | Web of Science | Medline5
Hellerstrom C . The life story of the pancreatic B cell. Diabetologia 1984;26:393-400
CrossRef | Web of Science | Medline6
Donath MY ,Halban PA . Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia 2004;47:581-589
CrossRef | Web of Science | Medline7
Dinarello CA . Biologic basis for interleukin-1 in disease. Blood 1996;87:2095-2147
Web of Science | Medline8
Mandrup-Poulsen T . The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 1996;39:1005-1029
CrossRef | Web of Science | Medline9
Bendtzen K ,Mandrup-Poulsen T ,Nerup J ,Nielsen JH ,Dinarello CA ,Svenson M . Cytotoxicity of human pI 7 interleukin-1 for pancreatic islets of Langerhans. Science 1986;232:1545-1547
CrossRef | Web of Science | Medline10
Maedler K ,Sergeev P ,Ris F , et al. Glucose-induced beta-cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002;110:851-860
Web of Science | Medline11
Maedler K ,Spinas GA ,Lehmann R , et al. Glucose induces beta-cell apoptosis via upregulation of the Fas-receptor in human islets. Diabetes 2001;50:1683-1690
CrossRef | Web of Science | Medline12
Maedler K ,Storling J ,Sturis J , et al. Glucose- and interleukin-1beta-induced beta-cell apoptosis requires Ca2+ influx and extracellular signal-regulated kinase (ERK) 1/2 activation and is prevented by a sulfonylurea receptor 1/inwardly rectifying K+ channel 6.2 (SUR/Kir6.2) selective potassium channel opener in human islets. Diabetes 2004;53:1706-1713
CrossRef | Web of Science | Medline13
Welsh N ,Cnop M ,Kharroubi I , et al. Is there a role for locally produced interleukin-1 in the deleterious effects of high glucose or the type 2 diabetes milieu to human pancreatic islets? Diabetes 2005;54:3238-3244
CrossRef | Web of Science | Medline14
Dinarello CA . The role of the interleukin-1-receptor antagonist in blocking inflammation mediated by interleukin-1. N Engl J Med 2000;343:732-734
Full Text | Web of Science | Medline15
Zumsteg U ,Reimers JI ,Pociot F , et al. Differential interleukin-1 receptor antagonism on pancreatic beta and alpha cells: studies in rodent and human islets and in normal rats. Diabetologia 1993;36:759-766
CrossRef | Web of Science | Medline16
Maedler K ,Sergeev P ,Ehses JA , et al. Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc Natl Acad Sci U S A 2004;101:8138-8143
CrossRef | Web of Science | Medline17
American Diabetes Association
Web of Science | Medline18
Vaag A ,Alford F ,Henriksen FL ,Christopher M ,Beck-Nielsen H . Multiple defects of both hepatic and peripheral intracellular glucose processing contribute to the hyperglycaemia of NIDDM. Diabetologia 1995;38:326-336
CrossRef | Web of Science | Medline19
Mootha VK ,Lindgren CM ,Eriksson KF , et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003;34:267-273
CrossRef | Web of Science | Medline20
Ling C ,Poulsen P ,Carlsson E , et al. Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest 2004;114:1518-1526
Web of Science | Medline21
Andersen L ,Dinesen B ,Jorgensen PN ,Poulsen F ,Roder ME . Enzyme immunoassay for intact human insulin in serum or plasma. Clin Chem 1993;39:578-582
Web of Science | Medline22
Hartling SG ,Dinesen B ,Kappelgard AM ,Faber OK ,Binder C . ELISA for human proinsulin. Clin Chim Acta 1986;156:289-297
CrossRef | Web of Science | Medline23
Heding LG . Radioimmunological determination of human C-peptide in serum. Diabetologia 1975;11:541-548
CrossRef | Web of Science | Medline24
Wallace TM ,Levy JC ,Matthews DR . Use and abuse of HOMA modeling. Diabetes Care 2004;27:1487-1495
CrossRef | Web of Science | Medline25
Goldbach-Mansky R ,Dailey NJ ,Canna SW , et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition. N Engl J Med 2006;355:581-592
Full Text | Web of Science | Medline26
Garcia MC ,Wernstedt I ,Berndtsson A , et al. Mature-onset obesity in interleukin-1 receptor I knockout mice. Diabetes 2006;55:1205-1213
CrossRef | Web of Science | Medline27
Chida D ,Osaka T ,Hashimoto O ,Iwakura Y . Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice. Diabetes 2006;55:971-977
CrossRef | Web of Science | Medline28
Dinarello CA . The many worlds of reducing interleukin-1. Arthritis Rheum 2005;52:1960-1967
CrossRef | Web of Science | Medline
- Citing Articles (239)
Citing Articles
1
Suyoung Bae, Jida Choi, Jaewoo Hong, Hyunjhung Jhun, Kwangwon Hong, Taebong Kang, Keeho Song, Sangmin Jeong, Hokee Yum, Soohyun Kim. (2012) Neutrophil Proteinase 3 Induces Diabetes in a Mouse Model of Glucose Tolerance. Endocrine Research 37:1, 35-45
CrossRef2
Till Strowig, Jorge Henao-Mejia, Eran Elinav, Richard Flavell. (2012) Inflammasomes in health and disease. Nature 481:7381, 278-286
CrossRef3
Shawn Winer, Daniel A Winer. (2012) The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance. Immunology and Cell Biology
CrossRef4
Hongming Miao, Yang Zhang, Zhongyan Lu, Qin Liu, Lixia Gan. (2012) FOXO1 involvement in insulin resistance-related pro-inflammatory cytokine production in hepatocytes. Inflammation Research
CrossRef5
Daniel J. Rader. (2012) IL-1 and atherosclerosis: a murine twist to an evolving human story. Journal of Clinical Investigation 122:1, 27-30
CrossRef6
B. Brooks-Worrell, J. P. Palmer. (2012) Immunology in the Clinic Review Series; focus on metabolic diseases: development of islet autoimmune disease in type 2 diabetes patients: potential sequelae of chronic inflammation. Clinical & Experimental Immunology 167:1, 40-46
CrossRef7
Rinke Stienstra, Cees J. Tack, Thirumala-Devi Kanneganti, Leo A.B. Joosten, Mihai G. Netea. (2012) The Inflammasome Puts Obesity in the Danger Zone. Cell Metabolism 15:1, 10-18
CrossRef8
Jeffrey H. Dunn, Lixia Z. Ellis, Mayumi Fujita. (2012) Inflammasomes as molecular mediators of inflammation and cancer: Potential role in melanoma. Cancer Letters 314:1, 24-33
CrossRef9
Michael J. Stuart, Bernhard T. Baune. (2012) Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neuroscience & Biobehavioral Reviews 36:1, 658-676
CrossRef10
Chia-Chao Wu, Huey-Kang Sytwu, Yuh-Feng Lin. 2012. Cytokines in diabetic nephropathy. , 55-74.
CrossRef11
M Dagenais, A Skeldon, M Saleh. (2012) The inflammasome: in memory of Dr. Jurg Tschopp. Cell Death and Differentiation 19:1, 5-12
CrossRef12
Namrata Iyer, Sandhya A. Marathe, Debalina Chaudhuri, Preeti Garai, Dipshikha Chakravortty. (2012) Immunomodulation using agonists and antagonists: potential clinical applications. Expert Opinion on Investigational Drugs 21:1, 67-81
CrossRef13
Karen K. Ryan, Stephen C. Woods, Randy J. Seeley. (2012) Central Nervous System Mechanisms Linking the Consumption of Palatable High-Fat Diets to the Defense of Greater Adiposity. Cell Metabolism
CrossRef14
Muhammad Sajid Hamid Akash, Qi Shen, Kanwal Rehman, Shuqing Chen. (2012) Interleukin-1 receptor antagonist: A new therapy for type 2 diabetes mellitus. Journal of Pharmaceutical Sciencesn/a-n/a
CrossRef15
Kitty P. Cheung, Kristen R. Taylor, Julie M. Jameson. (2011) Immunomodulation at epithelial sites by obesity and metabolic disease. Immunologic Research
CrossRef16
Simon Schenk, Olivia Osborn, Jerrold Olefsky. 2011. Mechanisms Mediating Obesity-Induced Inflammation and Insulin Resistance. , 199-214.
CrossRef17
Heidi Wolden-Kirk, Lut Overbergh, Henrik Thybo Christesen, Klaus Brusgaard, Chantal Mathieu. (2011) Vitamin D and diabetes: Its importance for beta cell and immune function. Molecular and Cellular Endocrinology 347:1-2, 106-120
CrossRef18
Yong Zhao, Zhaoshun Jiang, Chengshan Guo. (2011) New hope for type 2 diabetics: Targeting insulin resistance through the immune modulation of stem cells. Autoimmunity Reviews 11:2, 137-142
CrossRef19
James W. Ramadan, Stephen R. Steiner, Christina M. O’Neill, Craig S. Nunemaker. (2011) The central role of calcium in the effects of cytokines on beta-cell function: Implications for type 1 and type 2 diabetes. Cell Calcium 50:6, 481-490
CrossRef20
M. Lienhard Schmitz, Axel Weber, Thomas Roxlau, Matthias Gaestel, Michael Kracht. (2011) Signal integration, crosstalk mechanisms and networks in the function of inflammatory cytokines. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1813:12, 2165-2175
CrossRef21
Linda Rossi-Semerano, Isabelle Koné-Paut. (2011) Focus sur les inhibiteurs de l’interleukine 1. Revue du Rhumatisme Monographies
CrossRef22
Dongsheng Cai, Tiewen Liu. (2011) Hypothalamic inflammation: a double-edged sword to nutritional diseases. Annals of the New York Academy of Sciences 1243:1, E1-E39
CrossRef23
S. Graf, P.-M. Schumm-Draeger. (2011) Diabetes und Rheuma. Zeitschrift für Rheumatologie 70:9, 747-751
CrossRef24
Tetsu Miyamoto, Juan J. Carrero, Peter Stenvinkel. (2011) Inflammation as a risk factor and target for therapy in chronic kidney disease. Current Opinion in Nephrology and Hypertension 20:6, 662-668
CrossRef25
Kathryn M. Sumpter, Soumya Adhikari, Ellen K. Grishman, Perrin C. White. (2011) Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes. Pediatric Diabetes 12:7, 656-667
CrossRef26
Herbert Tilg, Alexander R. Moschen. (2011) IL-1 cytokine family members and NAFLD: Neglected in metabolic liver inflammation. Journal of Hepatology 55:5, 960-962
CrossRef27
Raphaela Goldbach-Mansky. (2011) Update on Monogenic Autoinflammatory diseases: The role of IL-1 and an emerging role for cytokines beyond IL-1 …. Clinical & Experimental Immunologyno-no
CrossRef28
B. Becattini, R. Marone, F. Zani, D. Arsenijevic, J. Seydoux, J.-P. Montani, A. G. Dulloo, B. Thorens, F. Preitner, M. P. Wymann, G. Solinas. (2011) PNAS Plus: PI3K within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance. Proceedings of the National Academy of Sciences 108:42, E854-E863
CrossRef29
M. F. Bachmann, G. T. Jennings. (2011) Therapeutic vaccines for chronic diseases: successes and technical challenges. Philosophical Transactions of the Royal Society B: Biological Sciences 366:1579, 2815-2822
CrossRef30
P. Menu, J. E. Vince. (2011) The NLRP3 inflammasome in health and disease: the good, the bad and the ugly. Clinical & Experimental Immunology 166:1, 1-15
CrossRef31
Allan Lawrie, Abdul G. Hameed, Janet Chamberlain, Nadine Arnold, Aneurin Kennerley, Kay Hopkinson, Josephine Pickworth, David G. Kiely, David C. Crossman, Sheila E. Francis. (2011) Paigen Diet–Fed Apolipoprotein E Knockout Mice Develop Severe Pulmonary Hypertension in an Interleukin-1–Dependent Manner. The American Journal of Pathology 179:4, 1693-1705
CrossRef32
Paul M Ridker, Tom Thuren, Andrew Zalewski, Peter Libby. (2011) Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: Rationale and Design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). American Heart Journal 162:4, 597-605
CrossRef33
Kristof Kersse, Mathieu J.M. Bertrand, Mohamed Lamkanfi, Peter Vandenabeele. (2011) NOD-like receptors and the innate immune system: Coping with danger, damage and death. Cytokine & Growth Factor Reviews 22:5-6, 257-276
CrossRef34
M. McCall, R. Pawlick, T. Kin, A. M. J. Shapiro. (2011) Anakinra Potentiates the Protective Effects of Etanercept in Transplantation of Marginal Mass Human Islets in Immunodeficient Mice. American Journal of Transplantationno-no
CrossRef35
Chun Zeng, Xiaoyun Shi, Baojun Zhang, He Liu, Lianjun Zhang, Wenjun Ding, Yong Zhao. (2011) The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. Journal of Molecular Medicine
CrossRef36
Sirish K Ippagunta, R K Subbarao Malireddi, Patrick J Shaw, Geoffrey A Neale, Lieselotte Vande Walle, Douglas R Green, Yoshinori Fukui, Mohamed Lamkanfi, Thirumala-Devi Kanneganti. (2011) The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization. Nature Immunology 12:10, 1010-1016
CrossRef37
Kenneth L. Rock, Jiann-Jyh Lai, Hajime Kono. (2011) Innate and adaptive immune responses to cell death. Immunological Reviews 243:1, 191-205
CrossRef38
M-H. Giroix, J-C. Irminger, G. Lacraz, C. Noll, S. Calderari, J. A. Ehses, J. Coulaud, M. Cornut, N. Kassis, F. Schmidlin, J-L. Paul, M. Kergoat, N. Janel, P. A. Halban, F. Homo-Delarche. (2011) Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto–Kakizaki (GK) rat. Diabetologia 54:9, 2451-2462
CrossRef39
Mohamed Lamkanfi, Lieselotte Vande Walle, Thirumala-Devi Kanneganti. (2011) Deregulated inflammasome signaling in disease. Immunological Reviews 243:1, 163-173
CrossRef40
Jaklien C. Leemans, Suzanne L. Cassel, Fayyaz S. Sutterwala. (2011) Sensing damage by the NLRP3 inflammasome. Immunological Reviews 243:1, 152-162
CrossRef41
Dario Tuccinardi, Elvira Fioriti, Silvia Manfrini, Eugenio D'Amico, Paolo Pozzilli. (2011) DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes. Expert Opinion on Biological Therapy 11:9, 1233-1240
CrossRef42
Jaana Suvisaari, Britt-Marie Loo, Suoma E. Saarni, Jari Haukka, Jonna Perälä, Samuli I. Saarni, Satu Viertiö, Krista Partti, Jouko Lönnqvist, Antti Jula. (2011) Inflammation in psychotic disorders: A population-based study. Psychiatry Research 189:2, 305-311
CrossRef43
Gillian M. Bell, Gary Reynolds, John D. Isaacs. (2011) Biologic therapies in non-rheumatic diseases: lessons for rheumatologists?. Nature Reviews Rheumatology 7:9, 507-516
CrossRef44
Aaron W. Michels, Matthias von Herrath. (2011) 2011 Update. Current Opinion in Endocrinology, Diabetes and Obesity 18:4, 235-240
CrossRef45
Dominic De Nardo, Eicke Latz. (2011) NLRP3 inflammasomes link inflammation and metabolic disease. Trends in Immunology 32:8, 373-379
CrossRef46
Göran K Hansson, Lars Klareskog. (2011) Pulling down the plug on atherosclerosis: Cooling down the inflammasome. Nature Medicine 17:7, 790-791
CrossRef47
KARSTEN BUSCHARD. (2011) What causes type 1 diabetes? Lessons from animal models. APMIS 119, 1-19
CrossRef48
Uchechukwu K Sampson, MacRae F Linton, Sergio Fazio. (2011) Are statins diabetogenic?. Current Opinion in Cardiology 26:4, 342-347
CrossRef49
Kazuki Mochizuki, Yasumi Misaki, Rie Miyauchi, Satsuki Takabe, Masaya Shimada, Noriyuki Miyoshi, Yoko Ichikawa, Toshinao Goda. (2011) Circulating interleukin-1β and interleukin-6 concentrations are closely associated with γ-glutamyltranspeptidase activity in middle-aged Japanese men without obvious cardiovascular diseases. Metabolism 60:7, 914-922
CrossRef50
, M. N. Pham, M. I. Hawa, C. Pfleger, M. Roden, G. Schernthaner, P. Pozzilli, R. Buzzetti, W. Scherbaum, J. Seissler, H. Kolb, S. Hunter, R. D. G. Leslie, N. C. Schloot. (2011) Pro- and anti-inflammatory cytokines in latent autoimmune diabetes in adults, type 1 and type 2 diabetes patients: Action LADA 4. Diabetologia 54:7, 1630-1638
CrossRef51
J. B. Galloway, K. L. Hyrich, L. K. Mercer, W. G. Dixon, K. D. Watson, M. Lunt, , D. P. M. Symmons, . (2011) The risk of serious infections in patients receiving anakinra for rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology 50:7, 1341-1342
CrossRef52
Andrea Cignarella. (2011) Targeting interleukin-1ß hampers atherosclerosis progression – Is there great promise?. Atherosclerosis 217:1, 64-66
CrossRef53
Marianne Böni-Schnetzler, Marc Y Donath. (2011) Increased IL-1β activation, the culprit not only for defective insulin secretion but also for insulin resistance?. Cell Research 21:7, 995-997
CrossRef54
Nicolas Rapin, Erik Mosekilde, Ole Lund. (2011) Bistability in autoimmune diseases. Autoimmunity 44:4, 256-260
CrossRef55
Maria G. Pavlatou, George Mastorakos, Alexandra Margeli, Evangelia Kouskouni, Nicholas Tentolouris, Nikos Katsilambros, George P. Chrousos, Ioannis Papassotiriou. (2011) Angiotensin blockade in diabetic patients decreases insulin resistance-associated low-grade inflammation. European Journal of Clinical Investigation 41:6, 652-658
CrossRef56
Frank Waldron-Lynch, Kevan C. Herold. (2011) Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes. Nature Reviews Drug Discovery 10:6, 439-452
CrossRef57
B S Nikolajczyk, M Jagannathan-Bogdan, H Shin, R Gyurko. (2011) State of the union between metabolism and the immune system in type 2 diabetes. Genes and Immunity 12:4, 239-250
CrossRef58
Aaron W. Michels, George S. Eisenbarth. (2011) Immune intervention in type 1 diabetes. Seminars in Immunology 23:3, 214-219
CrossRef59
Carey N. Lumeng, Alan R. Saltiel. (2011) Inflammatory links between obesity and metabolic disease. Journal of Clinical Investigation 121:6, 2111-2117
CrossRef60
S. L. Masters, E. Latz, L. A. J. O'Neill. (2011) The Inflammasome in Atherosclerosis and Type 2 Diabetes. Science Translational Medicine 3:81, 81ps17-81ps17
CrossRef61
Augustine M K Choi, Kiichi Nakahira. (2011) Dampening insulin signaling by an NLRP3 'meta-flammasome'. Nature Immunology 12:5, 379-380
CrossRef62
Haitao Wen, Denis Gris, Yu Lei, Sushmita Jha, Lu Zhang, Max Tze-Han Huang, Willie June Brickey, Jenny P-Y Ting. (2011) Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nature Immunology 12:5, 408-415
CrossRef63
Seth L. Masters, Luke A.J. O’Neill. (2011) Disease-associated amyloid and misfolded protein aggregates activate the inflammasome. Trends in Molecular Medicine 17:5, 276-282
CrossRef64
Jürg Tschopp. (2011) Mitochondria: Sovereign of inflammation?. European Journal of Immunology 41:5, 1196-1202
CrossRef65
Charles A. Dinarello. (2011) A clinical perspective of IL-1β as the gatekeeper of inflammation. European Journal of Immunology 41:5, 1203-1217
CrossRef66
Margaret F. Gregor, Gökhan S. Hotamisligil. (2011) Inflammatory Mechanisms in Obesity. Annual Review of Immunology 29:1, 415-445
CrossRef67
Beckley K. Davis, Haitao Wen, Jenny P.-Y. Ting. (2011) The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases. Annual Review of Immunology 29:1, 707-735
CrossRef68
Michael P. Czech, Myriam Aouadi, Gregory J. Tesz. (2011) RNAi-based therapeutic strategies for metabolic disease. Nature Reviews Endocrinology 7:8, 473-484
CrossRef69
C. A. Dinarello. (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117:14, 3720-3732
CrossRef70
Klaus Kratochwill, Michael Lechner, Anton Michael Lichtenauer, Rebecca Herzog, Hans Christian Lederhuber, Christian Siehs, Michaela Endemann, Bernd Mayer, Andreas Rizzi, Christoph Aufricht. (2011) Interleukin-1 Receptor-Mediated Inflammation Impairs the Heat Shock Response of Human Mesothelial Cells. The American Journal of Pathology 178:4, 1544-1555
CrossRef71
Man Yu, Stewart J. Levine. (2011) Toll-like receptor 3, RIG-I-like receptors and the NLRP3 inflammasome: Key modulators of innate immune responses to double-stranded RNA viruses. Cytokine & Growth Factor Reviews 22:2, 63-72
CrossRef72
A. Börjesson, S.G. Rønn, A.E. Karlsen, N. Billestrup, S. Sandler. (2011) β-cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice. Immunology Letters 136:1, 74-79
CrossRef73
Gil Leibowitz, Nurit Kaiser, Erol Cerasi. (2011) β-Cell failure in type 2 diabetes. Journal of Diabetes Investigation 2:2, 82-91
CrossRef74
J. Ludvigsson, M. Hjorth, M. Chéramy, S. Axelsson, M. Pihl, G. Forsander, N.-Ö. Nilsson, B.-O. Samuelsson, T. Wood, J. Åman, E. Örtqvist, R. Casas. (2011) Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. Diabetologia 54:3, 634-640
CrossRef75
Mohamed Lamkanfi. (2011) Emerging inflammasome effector mechanisms. Nature Reviews Immunology 11:3, 213-220
CrossRef76
Zafar H Israili. (2011) Advances in the Treatment of Type 2 Diabetes Mellitus. American Journal of Therapeutics 18:2, 117-152
CrossRef77
R. Brian Stevens, James T. Lane, Brian P. Boerner, Clifford D. Miles, Theodore H. Rigley, John P. Sandoz, Kathleen J. Nielsen, Jill Y. Skorupa, Anna J. Skorupa, Bruce Kaplan, Lucile E. Wrenshall. (2011) Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia. Clinical Transplantationno-no
CrossRef78
Helen J. Lachmann, Pierre Quartier, Alexander So, Philip N. Hawkins. (2011) The emerging role of interleukin-1β in autoinflammatory diseases. Arthritis & Rheumatism 63:2, 314-324
CrossRef79
Patrick J. Shaw, Michael F. McDermott, Thirumala-Devi Kanneganti. (2011) Inflammasomes and autoimmunity. Trends in Molecular Medicine 17:2, 57-64
CrossRef80
Bolormaa Vandanmagsar, Yun-Hee Youm, Anthony Ravussin, Jose E Galgani, Krisztian Stadler, Randall L Mynatt, Eric Ravussin, Jacqueline M Stephens, Vishwa Deep Dixit. (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature Medicine 17:2, 179-188
CrossRef81
Marc Y. Donath, Steven E. Shoelson. (2011) Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology 11:2, 98-107
CrossRef82
James Galea, Kayode Ogungbenro, Sharon Hulme, Andrew Greenhalgh, Leon Aarons, Sylvia Scarth, Peter Hutchinson, Samantha Grainger, Andrew King, Stephen J Hopkins, Nancy Rothwell, Pippa Tyrrell. (2011) Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study. Journal of Cerebral Blood Flow & Metabolism 31:2, 439-447
CrossRef83
Diane Mathis, Steven E. Shoelson. (2011) Immunometabolism: an emerging frontier. Nature Reviews Immunology 11:2, 81-83
CrossRef84
Yeqing Tong, Li Cai, Renli Zhang, Yanwei Zhang, Shenghong Liu, Liangqiang Lin, Zhiguang Zhao, Yijie Geng, Jing Xu, Hong Fan, Juan Zhang, Katherine A. Mason, Jinquan Cheng, Zuxun Lu. (2011) A novel tailed primers protocol to identify the association of IL-4 and IL-1RN (receptor antagonist) gene variable number of tandem repeats polymorphisms with ischemic stroke in Chinese Han population. Clinica Chimica Acta 412:5-6, 486-488
CrossRef85
Michaela C Stanton, Shu-Cheng Chen, James V Jackson, Alberto Rojas-Triana, David Kinsley, Long Cui, Jay S Fine, Scott Greenfeder, Loretta A Bober, Chung-Her Jenh. (2011) Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice. Journal of Inflammation 8:1, 8
CrossRef86
Thor Ueland, Anders P. Jørgensen, Kristin Godang, Kristian J. Fougner, Pål Aukrust, Pia Burman, Jens Bollerslev. (2011) Interleukin 1 receptor antagonist is associated with changes in body composition during physiological GH substitution in patients with adult-onset growth hormone deficiency. Clinical Endocrinology 74:1, 60-66
CrossRef87
James M. Krueger, Jeannine A. Majde. 2011. Sleep and Host Defense. , 281-290.
CrossRef88
C. A. Dinarello. (2011) Blocking interleukin-1β in acute and chronic autoinflammatory diseases. Journal of Internal Medicine 269:1, 16-28
CrossRef89
Myung-Shik Lee. (2011) Role of Innate Immunity in Diabetes and Metabolism: Recent Progress in the Study of Inflammasomes. Immune Network 11:2, 95
CrossRef90
Rebecca G. Baker, Matthew S. Hayden, Sankar Ghosh. (2011) NF-κB, Inflammation, and Metabolic Disease. Cell Metabolism 13:1, 11-22
CrossRef91
Michael Inouye, Johannes Kettunen, Pasi Soininen, Kaisa Silander, Samuli Ripatti, Linda S Kumpula, Eija Hämäläinen, Pekka Jousilahti, Antti J Kangas, Satu Männistö, Markku J Savolainen, Antti Jula, Jaana Leiviskä, Aarno Palotie, Veikko Salomaa, Markus Perola, Mika Ala-Korpela, Leena Peltonen. (2010) Metabonomic, transcriptomic, and genomic variation of a population cohort. Molecular Systems Biology 6,
CrossRef92
Tobias Boettler, Matthias von Herrath. (2010) Immunotherapy of type 1 diabetes — How to rationally prioritize combination therapies in T1D. International Immunopharmacology 10:12, 1491-1495
CrossRef93
Mette Koefoed, Claus M. Larsen, Mirjam V. Faulenbach, Allan Vaag, Jan A. Ehses, Marc Y. Donath, James Norton McGuire, Flemming Pociot, Thomas Mandrup-Poulsen. (2010) Serum Proteome Pool Changes in Type 2 Diabetic Patients Treated with Anakinra. Clinical Proteomics 6:4, 153-161
CrossRef94
Rinke Stienstra, Leo A.B. Joosten, Tim Koenen, Berry van Tits, Janna A. van Diepen, Sjoerd A.A. van den Berg, Patrick C.N. Rensen, Peter J. Voshol, Giamilla Fantuzzi, Anneke Hijmans, Sander Kersten, Michael Müller, Wim B. van den Berg, Nico van Rooijen, Martin Wabitsch, Bart-Jan Kullberg, Jos W.M. van der Meer, Thirumala Kanneganti, Cees J. Tack, Mihai G. Netea. (2010) The Inflammasome-Mediated Caspase-1 Activation Controls Adipocyte Differentiation and Insulin Sensitivity. Cell Metabolism 12:6, 593-605
CrossRef95
Grace Y. Chen, Gabriel Nuñez. (2010) Sterile inflammation: sensing and reacting to damage. Nature Reviews Immunology 10:12, 826-837
CrossRef96
Laura R. Rekedal, Elena Massarotti, Rajesh Garg, Radhika Bhatia, Timothy Gleeson, Bing Lu, Daniel H. Solomon. (2010) Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases. Arthritis & Rheumatism 62:12, 3569-3573
CrossRef97
C. Garcia, B. Feve, P. Ferré, S. Halimi, H. Baizri, L. Bordier, G. Guiu, O. Dupuy, B. Bauduceau, H. Mayaudon. (2010) Diabetes and inflammation: Fundamental aspects and clinical implications. Diabetes & Metabolism 36:5, 327-338
CrossRef98
Kavita Nyalakonda, Tarang Sharma, Faramarz Ismail-Beigi. (2010) Preservation of Beta-Cell Function in Type 2 Diabetes. Endocrine Practice 16:6, 1038-1055
CrossRef99
A. Roeske-Nielsen, L. T. Dalgaard, J.-E. Månsson, K. Buschard. (2010) The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes. Diabetes/Metabolism Research and Reviews 26:8, 631-638
CrossRef100
Marc Y. Donath, Marianne Böni-Schnetzler. (2010) IL-1β Activation as a Response to Metabolic Disturbances. Cell Metabolism 12:5, 427-428
CrossRef101
Seth L Masters, Aisling Dunne, Shoba L Subramanian, Rebecca L Hull, Gillian M Tannahill, Fiona A Sharp, Christine Becker, Luigi Franchi, Eiji Yoshihara, Zhe Chen, Niamh Mullooly, Lisa A Mielke, James Harris, Rebecca C Coll, Kingston H G Mills, K Hun Mok, Philip Newsholme, Gabriel Nuñez, Junji Yodoi, Steven E Kahn, Ed C Lavelle, Luke A J O'Neill. (2010) Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nature Immunology 11:10, 897-904
CrossRef102
G. Leibowitz, E. Bachar, M. Shaked, A. Sinai, M. Ketzinel-Gilad, E. Cerasi, N. Kaiser. (2010) Glucose regulation of β-cell stress in type 2 diabetes. Diabetes, Obesity and Metabolism 12, 66-75
CrossRef103
John J. Taylor. (2010) Cytokine regulation of immune responses to Porphyromonas gingivalis. Periodontology 2000 54:1, 160-194
CrossRef104
Yasumi Misaki, Rie Miyauchi, Kazuki Mochizuki, Satsuki Takabe, Masaya Shimada, Yoko Ichikawa, Toshinao Goda. (2010) Plasma interleukin-1β concentrations are closely associated with fasting blood glucose levels in healthy and preclinical middle-aged nonoverweight and overweight Japanese men. Metabolism 59:10, 1465-1471
CrossRef105
, Johnny Ludvigsson. (2010) Immune Intervention in Children with Type 1 Diabetes. Current Diabetes Reports 10:5, 370-379
CrossRef106
Thomas Mandrup-Poulsen. (2010) IAPP boosts islet macrophage IL-1 in type 2 diabetes. Nature Immunology 11:10, 881-883
CrossRef107
Kari Luotola, Arto Pietilä, Mervi Alanne, Timo Lanki, Britt-Marie Loo, Antti Jula, Markus Perola, Annette Peters, Tanja Zeller, Stefan Blankenberg, Veikko Salomaa. (2010) Genetic variation of the interleukin-1 family and nongenetic factors determining the interleukin-1 receptor antagonist phenotypes. Metabolism 59:10, 1520-1527
CrossRef108
Manfred Kopf, Martin F. Bachmann, Benjamin J. Marsland. (2010) Averting inflammation by targeting the cytokine environment. Nature Reviews Drug Discovery 9:9, 703-718
CrossRef109
Juan J. Carrero, Peter Stenvinkel. (2010) Inflammation in End-Stage Renal Disease-What Have We Learned in 10 Years?. Seminars in Dialysis 23:5, 498-509
CrossRef110
Laurence Feldmeyer, Sabine Werner, Lars E. French, Hans-Dietmar Beer. (2010) Interleukin-1, inflammasomes and the skin. European Journal of Cell Biology 89:9, 638-644
CrossRef111
Hery Winarsi, Agus Purwanto. (2010) Soy Germed Protein Plus Zn as an Inducer Insulin Secretion on Type-2 Diabetes Mellitus. HAYATI Journal of Biosciences 17:3, 120-124
CrossRef112
I. Kötter, G. Horneff. (2010) IL-1-Antagonisten. Zeitschrift für Rheumatologie 69:7, 581-593
CrossRef113
Bente K. Pedersen, Mark A. Febbraio. (2010) Diabetes: Treatment of diabetes mellitus: new tricks by an old player. Nature Reviews Endocrinology 6:9, 482-483
CrossRef114
Khalida Ismail. 2010. Unraveling the Pathogenesis of the Depression-Diabetes Link. , 29-61.
CrossRef115
Cailin Henderson, Raphaela Goldbach-Mansky. (2010) Monogenic autoinflammatory diseases: new insights into clinical aspects and pathogenesis. Current Opinion in Rheumatology1
CrossRef116
J. A. Ehses, D. T. Meier, S. Wueest, J. Rytka, S. Boller, P. Y. Wielinga, A. Schraenen, K. Lemaire, S. Debray, L. Lommel, J. A. Pospisilik, O. Tschopp, S. M. Schultze, U. Malipiero, H. Esterbauer, H. Ellingsgaard, S. Rütti, F. C. Schuit, T. A. Lutz, M. Böni-Schnetzler, D. Konrad, Marc Y. Donath. (2010) Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet. Diabetologia 53:8, 1795-1806
CrossRef117
Srinath Sanda, Jenna Bollyky, Nathan Standifer, Gerald Nepom, Jessica A. Hamerman, Carla Greenbaum. (2010) Short-term IL-1β blockade reduces monocyte CD11b integrin expression in an IL-8 dependent fashion in patients with type 1 diabetes. Clinical Immunology 136:2, 170-173
CrossRef118
Usriansyah Hadis, Graham R. Leggatt, Ranjeny Thomas, Ian H. Frazer, Eva M. Kovacs. (2010) IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes. Experimental Dermatology 19:8, 723-729
CrossRef119
Daniel Eberhard, Martin Kragl, Eckhard Lammert. (2010) ‘Giving and taking’: endothelial and β-cells in the islets of Langerhans. Trends in Endocrinology & Metabolism 21:8, 457-463
CrossRef120
Mazen Alsahli, John E. Gerich. 2010. Abnormalities of Insulin Secretion and β-Cell Defects in Type 2 Diabetes. , 160-173.
CrossRef121
Edwina Naik, Vishva M. Dixit. (2010) Modulation of Inflammasome Activity for the Treatment of Auto-inflammatory Disorders. Journal of Clinical Immunology 30:4, 485-490
CrossRef122
M. Igoillo-Esteve, L. Marselli, D. A. Cunha, L. Ladrière, F. Ortis, F. A. Grieco, F. Dotta, G. C. Weir, P. Marchetti, D. L. Eizirik, M. Cnop. (2010) Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 53:7, 1395-1405
CrossRef123
M. Jagannathan, M. McDonnell, Y. Liang, H. Hasturk, J. Hetzel, D. Rubin, A. Kantarci, T. E. Dyke, L. M. Ganley-Leal, B. S. Nikolajczyk. (2010) Toll-like receptors regulate B cell cytokine production in patients with diabetes. Diabetologia 53:7, 1461-1471
CrossRef124
Greta Guarda, Alexander So. (2010) Regulation of inflammasome activity. Immunology 130:3, 329-336
CrossRef125
Gaurav Verma, Malabika Datta. (2010) IL-1β induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells. Apoptosis 15:7, 864-876
CrossRef126
Edward D. Siew, Talat Alp Ikizler. (2010) Insulin Resistance and Protein Energy Metabolism in Patients with Advanced Chronic Kidney Disease. Seminars in Dialysis 23:4, 378-382
CrossRef127
Charles A Dinarello, Marc Y Donath, Thomas Mandrup-Poulsen. (2010) Role of IL-1β in type 2 diabetes. Current Opinion in Endocrinology, Diabetes and Obesity1
CrossRef128
Cormac Sheridan. (2010) Firms chase diabetic inflammation with anti-IL-1β antibodies. Nature Biotechnology 28:6, 533-534
CrossRef129
Huw Bowen Jones, David Nugent, Richard Jenkins. (2010) Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains. International Journal of Experimental Pathology 91:3, 288-301
CrossRef130
Bernhard Maier, Takeshi Ogihara, Anthony P. Trace, Sarah A. Tersey, Reiesha D. Robbins, Swarup K. Chakrabarti, Craig S. Nunemaker, Natalie D. Stull, Catherine A. Taylor, John E. Thompson, Richard S. Dondero, Eli C. Lewis, Charles A. Dinarello, Jerry L. Nadler, Raghavendra G. Mirmira. (2010) The unique hypusine modification of eIF5A promotes islet β cell inflammation and dysfunction in mice. Journal of Clinical Investigation 120:6, 2156-2170
CrossRef131
Ioannis Mitroulis, Panagiotis Skendros, Konstantinos Ritis. (2010) Targeting IL-1β in disease; the expanding role of NLRP3 inflammasome. European Journal of Internal Medicine 21:3, 157-163
CrossRef132
Giuseppe Matarese, Claudio Procaccini, Veronica De Rosa, Tamas L. Horvath, Antonio La Cava. (2010) Regulatory T cells in obesity: the leptin connection. Trends in Molecular Medicine 16:6, 247-256
CrossRef133
Janine K Kruit, Liam R Brunham, C Bruce Verchere, Michael R Hayden. (2010) HDL and LDL cholesterol significantly influence β-cell function in type 2 diabetes mellitus. Current Opinion in Lipidology 21:3, 178-185
CrossRef134
JOHANNA SAHLMAN, KATI MIETTINEN, KEIJO PEUHKURINEN, JUHA SEPPÄ, MARKKU PELTONEN, CHRISTIAN HERDER, KARI PUNNONEN, ESKO VANNINEN, HELENA GYLLING, MARKKU PARTINEN, MATTI UUSITUPA, HENRI TUOMILEHTO, . (2010) The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea. Journal of Sleep Research 19:2, 341-348
CrossRef135
Charles A. Dinarello. (2010) Why not treat human cancer with interleukin-1 blockade?. Cancer and Metastasis Reviews 29:2, 317-329
CrossRef136
Marc Y. Donath, Marianne Böni-Schnetzler, Helga Ellingsgaard, Philippe A. Halban, Jan A. Ehses. (2010) Cytokine production by islets in health and diabetes: cellular origin, regulation and function. Trends in Endocrinology & Metabolism 21:5, 261-267
CrossRef137
Cailin Henderson, Raphaela Goldbach-Mansky. (2010) Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: Finding the right balance in response to danger signals. Clinical Immunology 135:2, 210-222
CrossRef138
Cem Gabay, Céline Lamacchia, Gaby Palmer. (2010) IL-1 pathways in inflammation and human diseases. Nature Reviews Rheumatology 6:4, 232-241
CrossRef139
Takeshi Ogihara, Raghavendra G Mirmira. (2010) An islet in distress: β cell failure in type 2 diabetes. Journal of Diabetes Investigation
CrossRef140
Katherine A. Fitzgerald. (2010) NLR-containing inflammasomes: Central mediators of host defense and inflammation. European Journal of Immunology 40:3, 595-598
CrossRef141
Charles A. Dinarello. (2010) Anti-inflammatory Agents: Present and Future. Cell 140:6, 935-950
CrossRef142
Jerrold M. Olefsky, Christopher K. Glass. (2010) Macrophages, Inflammation, and Insulin Resistance. Annual Review of Physiology 72:1, 219-246
CrossRef143
Kate Schroder, Jurg Tschopp. (2010) The Inflammasomes. Cell 140:6, 821-832
CrossRef144
Thomas Mandrup-Poulsen, Linda Pickersgill, Marc Yves Donath. (2010) Blockade of interleukin 1 in type 1 diabetes mellitus. Nature Reviews Endocrinology 6:3, 158-166
CrossRef145
Virginia Pascual, Damien Chaussabel, Jacques Banchereau. (2010) A Genomic Approach to Human Autoimmune Diseases. Annual Review of Immunology 28:1, 535-571
CrossRef146
Graham P. Cook, Sinisa Savic, Miriam Wittmann, Michael F. McDermott. (2010) The NLRP3 inflammasome, a target for therapy in diverse disease states. European Journal of Immunology 40:3, 631-634
CrossRef147
Daniel L. Kastner, Ivona Aksentijevich, Raphaela Goldbach-Mansky. (2010) Autoinflammatory Disease Reloaded: A Clinical Perspective. Cell 140:6, 784-790
CrossRef148
Charles A. Dinarello. (2010) IL-1: Discoveries, controversies and future directions. European Journal of Immunology 40:3, 599-606
CrossRef149
Cristina M. Sena, Carla F. Bento, Paulo Pereira, Raquel Seiça. (2010) Diabetes mellitus: new challenges and innovative therapies. The EPMA Journal 1:1, 138-163
CrossRef150
Abishek Iyer, David P. Fairlie, Johannes B. Prins, Bruce D. Hammock, Lindsay Brown. (2010) Inflammatory lipid mediators in adipocyte function and obesity. Nature Reviews Endocrinology 6:2, 71-82
CrossRef151
Rongbin Zhou, Aubry Tardivel, Bernard Thorens, Inpyo Choi, Jürg Tschopp. (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunology 11:2, 136-140
CrossRef152
Peter C. Austin, Andrea Manca, Merrick Zwarenstein, David N. Juurlink, Matthew B. Stanbrook. (2010) A substantial and confusing variation exists in handling of baseline covariates in randomized controlled trials: a review of trials published in leading medical journals. Journal of Clinical Epidemiology 63:2, 142-153
CrossRef153
Beckley K Davis, Jenny Pan-Yun Ting. (2010) NLRP3 has a sweet tooth. Nature Immunology 11:2, 105-106
CrossRef154
John E. Sims, Dirk E. Smith. (2010) The IL-1 family: regulators of immunity. Nature Reviews Immunology 10:2, 117
CrossRef155
K. Schroder, R. Zhou, J. Tschopp. (2010) The NLRP3 Inflammasome: A Sensor for Metabolic Danger?. Science 327:5963, 296-300
CrossRef156
H. Kolb, T. Mandrup-Poulsen. (2010) The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia 53:1, 10-20
CrossRef157
Chunjiong Wang, Youfei Guan, Jichun Yang. (2010) Cytokines in the Progression of Pancreatic β-Cell Dysfunction. International Journal of Endocrinology 2010, 1-10
CrossRef158
Peter Sommer, Gary Sweeney. (2010) Functional and Mechanistic Integration of Infection and the Metabolic Syndrome. Korean Diabetes Journal 34:2, 71
CrossRef159
Aidan Ryan, Madeline Murphy, Catherine Godson, Fionnuala B. Hickey. (2009) Diabetes mellitus and apoptosis: inflammatory cells. Apoptosis 14:12, 1435-1450
CrossRef160
J. M. R. Gill, N. Sattar. (2009) Ceramides: A new player in the inflammation–insulin resistance paradigm?. Diabetologia 52:12, 2475-2477
CrossRef161
Leo A. B. Joosten, Mihai G. Netea, Giamila Fantuzzi, Marije I. Koenders, Monique M. A. Helsen, Helmut Sparrer, Christine T. Pham, Jos W. M. van der Meer, Charles A. Dinarello, Wim B. van den Berg. (2009) Inflammatory arthritis in caspase 1 geneâdeficient mice: Contribution of proteinase 3 to caspase 1âindependent production of bioactive interleukin-1β. Arthritis & Rheumatism 60:12, 3651-3662
CrossRef162
Anil Bhansali, Vimal Upreti, N. Khandelwal, N. Marwaha, Vivek Gupta, Naresh Sachdeva, R.R. Sharma, Karan Saluja, Pinaki Dutta, Rama Walia, Ranjana Minz, Sanjay Bhadada, Sambit Das, Santosh Ramakrishnan. (2009) Efficacy of Autologous Bone Marrow–Derived Stem Cell Transplantation in Patients With Type 2 Diabetes Mellitus. Stem Cells and Development 18:10, 1407-1416
CrossRef163
Raphaela Goldbach-Mansky. (2009) Blocking Interleukin-1 in Rheumatic Diseases. Annals of the New York Academy of Sciences 1182:1, 111-123
CrossRef164
Raphaela Goldbach-Mansky, Daniel L. Kastner. (2009) Autoinflammation: The prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. Journal of Allergy and Clinical Immunology 124:6, 1141-1149
CrossRef165
Kathleen Coyle, Kristina I. Rother, Martina Weise, Alaa Ahmed, Frederick W. Miller, Lisa G. Rider. (2009) Metabolic Abnormalities and Cardiovascular Risk Factors in Children with Myositis. The Journal of Pediatrics 155:6, 882-887
CrossRef166
J. C. Jonas, M. Bensellam, J. Duprez, H. Elouil, Y. Guiot, S. M. A. Pascal. (2009) Glucose regulation of islet stress responses and β-cell failure in type 2 diabetes. Diabetes, Obesity and Metabolism 11, 65-81
CrossRef167
Adiv Goldhaber, Rosane Ness-Abramof, Martin H. Ellis. (2009) Prevalence of Anemia Among Unselected Adults with Diabetes Mellitus and Normal Serum Creatinine Levels. Endocrine Practice 15:7, 714-719
CrossRef168
José Abrão Cardeal da Costa, T. Alp Ikizler. (2009) Inflammation and Insulin Resistance as Novel Mechanisms of Wasting in Chronic Dialysis Patients. Seminars in Dialysis 22:6, 652-657
CrossRef169
S.D. Gadola. (2009) Interleukin-1-Zytokine, Inflammasome, NOD-Signalosome und Autoinflammation. Zeitschrift für Rheumatologie 68:9, 712-719
CrossRef170
Herbert Tilg, Alexander Moschen. 2009. Inflammatory and Anti-Inflammatory Mediators Secreted by Adipose Tissue. , 65-81.
CrossRef171
R. Paul Robertson. (2009) β-Cell deterioration during diabetes: what's in the gun?. Trends in Endocrinology & Metabolism 20:8, 388-393
CrossRef172
Jan A. Ehses, Helga Ellingsgaard, Marianne Böni-Schnetzler, Marc Y. Donath. (2009) Pancreatic islet inflammation in type 2 diabetes: From α and β cell compensation to dysfunction. Archives Of Physiology And Biochemistry 115:4, 240-247
CrossRef173
Robert W. O’Rourke. (2009) Molecular Mechanisms of Obesity and Diabetes: At the Intersection of Weight Regulation, Inflammation, and Glucose Homeostasis. World Journal of Surgery 33:10, 2007-2013
CrossRef174
Katia P. Karalis, Panagiotis Giannogonas, Elisavet Kodela, Yassemi Koutmani, Manolis Zoumakis, Thalia Teli. (2009) Mechanisms of obesity and related pathology: linking immune responses to metabolic stress. FEBS Journal 276:20, 5747-5754
CrossRef175
John M. Wentworth, Spiros Fourlanos, Leonard C. Harrison. (2009) Reappraising the stereotypes of diabetes in the modern diabetogenic environment. Nature Reviews Endocrinology 5:9, 483-489
CrossRef176
Yuji Tajiri, Mikako Kimura, Kazuo Mimura, Fumio Umeda. (2009) Variation of Fasting Serum C-Peptide Level After Admission in Japanese Patients with Type 2 Diabetes Mellitus. Diabetes Technology & Therapeutics 11:9, 593-599
CrossRef177
J. A. Ehses, G. Lacraz, M.-H. Giroix, F. Schmidlin, J. Coulaud, N. Kassis, J.-C. Irminger, M. Kergoat, B. Portha, F. Homo-Delarche, M. Y. Donath. (2009) IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proceedings of the National Academy of Sciences 106:33, 13998-14003
CrossRef178
Alice Schwarznau, Matthew S. Hanson, Jamie M. Sperger, Brian R. Schram, Juan S. Danobeitia, Krista K. Greenwood, Ashwanth Vijayan, Luis A. Fernandez. (2009) IL-1β receptor blockade protects islets against pro-inflammatory cytokine induced necrosis and apoptosis. Journal of Cellular Physiology 220:2, 341-347
CrossRef179
Bernhard O. Boehm, Silke Rosinger, Guido Sauer, Burkhard J. Manfras, David Palesch, Stefan Schiekofer, Hubert Kalbacher, Timo Burster. (2009) Protease-resistant human GAD-derived altered peptide ligands decrease TNF-α and IL-17 production in peripheral blood cells from patients with type 1 diabetes mellitus. Molecular Immunology 46:13, 2576-2584
CrossRef180
R. Glas, N. S. Sauter, F. T. Schulthess, L. Shu, J. Oberholzer, K. Maedler. (2009) Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival. Diabetologia 52:8, 1579-1588
CrossRef181
Dinarello, Charles A., . (2009) Interleukin-1β and the Autoinflammatory Diseases. New England Journal of Medicine 360:23, 2467-2470
Full Text182
Martin Blixt, Bo Niklasson, Stellan Sandler. (2009) Suppression of bank vole pancreatic islet function by proinflammatory cytokines. Molecular and Cellular Endocrinology 305:1-2, 1-5
CrossRef183
Patrizia Bottoni, Bruno Giardina, Roberto Scatena. (2009) Proteomic profiling of heat shock proteins: An emerging molecular approach with direct pathophysiological and clinical implications. PROTEOMICS - CLINICAL APPLICATIONS 3:6, 636-653
CrossRef184
Bruno Fève, Jean-Philippe Bastard. (2009) The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nature Reviews Endocrinology 5:6, 305-311
CrossRef185
Adam Kaufman, Kevan C. Herold. (2009) Anti-CD3 mAbs for treatment of type 1 diabetes. Diabetes/Metabolism Research and Reviews 25:4, 302-306
CrossRef186
N Andersson, L Strandberg, S Nilsson, Ö Ljungren, M K Karlsson, D Mellström, M Lorentzon, C Ohlsson, J-O Jansson. (2009) Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men. International Journal of Obesity 33:5, 525-533
CrossRef187
Paolo Pozzilli, R. David Leslie. (2009) New prospects for immunotherapy at diagnosis of type 1 diabetes. Diabetes/Metabolism Research and Reviews 25:4, 299-301
CrossRef188
Linda M.S. Pickersgill, Thomas R. Mandrup-Poulsen. (2009) The anti-interleukin-1 in type 1 diabetes action trial-background and rationale. Diabetes/Metabolism Research and Reviews 25:4, 321-324
CrossRef189
Anna Ryden, Katerina Stechova, Marianna Durilova, Maria Faresjö. (2009) Switch from a dominant Th1-associated immune profile during the pre-diabetic phase in favour of a temporary increase of a Th3-associated and inflammatory immune profile at the onset of type 1 diabetes. Diabetes/Metabolism Research and Reviews 25:4, 335-343
CrossRef190
Lobelia Samavati, Ruchi Rastogi, Wenjin Du, Maik Hüttemann, Alemu Fite, Luigi Franchi. (2009) STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria. Molecular Immunology 46:8-9, 1867-1877
CrossRef191
Susan Kralisch, Sebastian Weise, Grit Sommer, Jana Lipfert, Ulrike Lossner, Matthias Bluher, Michael Stumvoll, Mathias Fasshauer. (2009) Interleukin-1ß induces the novel adipokine chemerin in adipocytes in vitro. Regulatory Peptides 154:1-3, 102-106
CrossRef192
Charles A. Dinarello. (2009) Immunological and Inflammatory Functions of the Interleukin-1 Family. Annual Review of Immunology 27:1, 519-550
CrossRef193
Steven E Shoelson, Allison B Goldfine. (2009) Getting away from glucose: fanning the flames of obesity-induced inflammation. Nature Medicine 15:4, 373-374
CrossRef194
Seth L. Masters, Anna Simon, Ivona Aksentijevich, Daniel L. Kastner. (2009) Horror Autoinflammaticus : The Molecular Pathophysiology of Autoinflammatory Disease *. Annual Review of Immunology 27:1, 621-668
CrossRef195
Joachim R Kalden, Harald Burkhardt. 2009. Autoimmune Disease: Treatment. .
CrossRef196
Robert W. O'Rourke. (2009) Inflammation in obesity-related diseases. Surgery 145:3, 255-259
CrossRef197
Gary T. Jennings, Martin F. Bachmann. (2009) Immunodrugs: Therapeutic VLP-Based Vaccines for Chronic Diseases. Annual Review of Pharmacology and Toxicology 49:1, 303-326
CrossRef198
Grit Sommer, Sebastian Weise, Susan Kralisch, Ulrike Lossner, Matthias Bluher, Michael Stumvoll, Mathias Fasshauer. (2009) Lipocalin-2 is induced by interleukin-1β in murine adipocytes in vitro. Journal of Cellular Biochemistry 106:1, 103-108
CrossRef199
Axel J. Hueber, Iain B. McInnes. 2009. Pathogenesis in Rheumatoid Arthritis: Cytokines. , 200-208.
CrossRef200
S. Rafiq, D. Melzer, M. N. Weedon, H. Lango, R. Saxena, L. J. Scott, , C. N. A. Palmer, A. D. Morris, M. I. McCarthy, L. Ferrucci, A. T. Hattersley, E. Zeggini, T. M. Frayling. (2008) Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes. Diabetologia 51:12, 2205-2213
CrossRef201
M. Böni-Schnetzler, J. A. Ehses, M. Faulenbach, M. Y. Donath. (2008) Insulitis in type 2 diabetes. Diabetes, Obesity and Metabolism 10, 201-204
CrossRef202
P. A. Halban. (2008) Cell therapy for type 2 diabetes: is it desirable and can we get it?. Diabetes, Obesity and Metabolism 10, 205-211
CrossRef203
E. C. Lewis, M. Mizrahi, M. Toledano, N. DeFelice, J. L. Wright, A. Churg, L. Shapiro, C. A. Dinarello. (2008) 1-Antitrypsin monotherapy induces immune tolerance during islet allograft transplantation in mice. Proceedings of the National Academy of Sciences 105:42, 16236-16241
CrossRef204
S. G. Rønn, A. Börjesson, C. Bruun, P. E. Heding, H. Frobøse, T. Mandrup-Poulsen, A. E. Karlsen, J. Rasschaert, S. Sandler, N. Billestrup. (2008) Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection. Diabetologia 51:10, 1873-1882
CrossRef205
L. Mateos Polo, J.C. Hernández Criado, N. Cubino Bóveda, A. García Mingo. (2008) Antidiabéticos orales. Medicine - Programa de Formación Médica Continuada Acreditado 10:18, 1188-1194
CrossRef206
O. Osborn, S.E. Brownell, M. Sanchez-Alavez, D. Salomon, H. Gram, T. Bartfai. (2008) Treatment with an Interleukin 1 beta antibody improves glycemic control in diet-induced obesity. Cytokine 44:1, 141-148
CrossRef207
H. Ellingsgaard, J. A. Ehses, E. B. Hammar, L. Van Lommel, R. Quintens, G. Martens, J. Kerr-Conte, F. Pattou, T. Berney, D. Pipeleers, P. A. Halban, F. C. Schuit, M. Y. Donath. (2008) Interleukin-6 regulates pancreatic -cell mass expansion. Proceedings of the National Academy of Sciences 105:35, 13163-13168
CrossRef208
D. Chida, O. Hashimoto, M. Kuwahara, H. Sagara, T. Osaka, H. Tsubone, Y. Iwakura. (2008) Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone. Diabetologia 51:9, 1698-1706
CrossRef209
Grit Sommer, Sebastian Weise, Susan Kralisch, Philipp E. Scherer, Ulrike Lössner, Matthias Blüher, Michael Stumvoll, Mathias Fasshauer. (2008) The adipokine SAA3 is induced by interleukin-1β in mouse adipocytes. Journal of Cellular Biochemistry 104:6, 2241-2247
CrossRef210
Jennifer Bollyky, Srinath Sanda, Carla J. Greenbaum. (2008) Type 1 diabetes mellitus: primary, secondary, and tertiary prevention. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 75:4, 385-397
CrossRef211
L. Riem. (2008) Bewegung in der Therapie des Typ-2-Diabetes. Der Diabetologe 4:5, 368-371
CrossRef212
Basel al-Ramadi, Adrian Hayday, Wilhelm Schwaeble. (2008) Immunology in the Arabian desert. Nature Immunology 9:7, 699-703
CrossRef213
J A. Jeevendra Martyn, Masao Kaneki, Shingo Yasuhara. (2008) Obesity-induced Insulin Resistance and Hyperglycemia. Anesthesiology 109:1, 137-148
CrossRef214
J. Saltevo, M. Laakso, J. Jokelainen, S. Keinänen‐Kiukaanniemi, E. Kumpusalo, M. Vanhala. (2008) Levels of adiponectin, C‐reactive protein and interleukin‐1 receptor antagonist are associated with insulin sensitivity: a population‐based study. Diabetes/Metabolism Research and Reviews 24:5, 378-383
CrossRef215
Cecilia P. Chung, Annette Oeser, Joseph F. Solus, Tebeb Gebretsadik, Ayumi Shintani, Ingrid Avalos, Tuulikki Sokka, Paolo Raggi, Theodore Pincus, C. Michael Stein. (2008) Inflammation‐associated insulin resistance: Differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis & Rheumatism 58:7, 2105-2112
CrossRef216
A. Gangemi, P. Salehi, B. Hatipoglu, J. Martellotto, B. Barbaro, J. B. Kuechle, M. Qi, Y. Wang, P. Pallan, C. Owens, J. Bui, D. West, B. Kaplan, E. Benedetti, J. Oberholzer. (2008) Islet Transplantation for Brittle Type 1 Diabetes: The UIC Protocol. American Journal of Transplantation 8:6, 1250-1261
CrossRef217
N. Sattar, S. G. Wannamethee, N. G. Forouhi. (2008) Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities?. Diabetologia 51:6, 926-940
CrossRef218
Marc Y Donath, Thomas Mandrup-Poulsen. (2008) The use of interleukin-1-receptor antagonists in the treatment of diabetes mellitus. Nature Clinical Practice Endocrinology & Metabolism 4:5, 240-241
CrossRef219
Kyoichi Fukuda, Greg H Tesch, Felicia Y Yap, Josephine M Forbes, Richard A Flavell, Roger J Davis, David J Nikolic-Paterson. (2008) MKK3 signalling plays an essential role in leukocyte-mediated pancreatic injury in the multiple low-dose streptozotocin model. Laboratory Investigation 88:4, 398-407
CrossRef220
Anette-G. Ziegler, Markus Walter, Heike Boerschmann. (2008) Inflammation at the islets of Langerhans and its role for the pathogenesis of type 2 diabetes. Current Diabetes Reports 8:2, 85-86
CrossRef221
Joseph Tibaldi. (2008) Preserving insulin secretion in Type 2 diabetes mellitus. Expert Review of Endocrinology & Metabolism 3:2, 147-159
CrossRef222
George D Kalliolias, Stamatis-Nick C Liossis. (2008) The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis. Expert Opinion on Investigational Drugs 17:3, 349-359
CrossRef223
J. Ybarra, T.N.O. Lehmann, A. Golay, C.E. Juge-Aubry, P. Roux-Lombard, J.-M. Dayer, C.A. Meier. (2008) Gender-based dimorphic pattern for interleukin-1 receptor antagonist in type 2 diabetes mellitus. Diabetes & Metabolism 34:1, 75-81
CrossRef224
William P. Arend, Mary B. Goldring. (2008) The development of anticytokine therapeutics for rheumatic diseases. Arthritis & Rheumatism 58:S2, S102-S109
CrossRef225
José Manuel Fernández-Real, John C. Pickup. (2008) Innate immunity, insulin resistance and type 2 diabetes. Trends in Endocrinology & Metabolism 19:1, 10-16
CrossRef226
Eva Dahlén, Karin Barchan, Daniel Herrlander, Patrik Höjman, Marie Karlsson, Lill Ljung, Mats Andersson, Eva Bäckman, Ann-Christin Malmborg Hager, Björn Walse, Leo Joosten, Wim van den Berg. (2008) Development of Interleukin-1 Receptor Antagonist Mutants with Enhanced Antagonistic Activity In Vitro and Improved Therapeutic Efficacy in Collagen-Induced Arthritis. Journal of Immunotoxicology 5:2, 189-199
CrossRef227
Juan Jesus Carrero, Mahmut Ilker Yilmaz, Bengt Lindholm, Peter Stenvinkel. (2008) Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It?. Blood Purification 26:3, 291-299
CrossRef228
Fabrizio Montecucco, Sabine Steffens, François Mach. (2008) Insulin Resistance: A Proinflammatory State Mediated by Lipid-Induced Signaling Dysfunction and Involved in Atherosclerotic Plaque Instability. Mediators of Inflammation 2008, 1-10
CrossRef229
Nelly A Maybee, Bradford B Worrall, Jerry L Nadler. (2007) Is anti-inflammatory therapy for type 2 diabetes mellitus ready for routine clinical practice?. Nature Clinical Practice Endocrinology & Metabolism 3:12, 806-807
CrossRef230
Florence Allantaz, Damien Chaussabel, Jacques Banchereau, Virginia Pascual. (2007) Microarray-based identification of novel biomarkers in IL-1-mediated diseases. Current Opinion in Immunology 19:6, 623-632
CrossRef231
Heidi Ledford. (2007) Fever pitch. Nature 450:7170, 600-601
CrossRef232
Charles A. Dinarello. (2007) Historical insights into cytokines. European Journal of Immunology 37:S1, S34-S45
CrossRef233
Christoph Handschin, Cheol Soo Choi, Sherry Chin, Sheene Kim, Dan Kawamori, Amarnath J. Kurpad, Nicole Neubauer, Jiang Hu, Vamsi K. Mootha, Young-Bum Kim, Rohit N. Kulkarni, Gerald I. Shulman, Bruce M. Spiegelman. (2007) Abnormal glucose homeostasis in skeletal muscle–specific PGC-1α knockout mice reveals skeletal muscle–pancreatic β cell crosstalk. Journal of Clinical Investigation 117:11, 3463-3474
CrossRef234
Charles A. Dinarello. (2007) Mutations in cryopyrin: Bypassing roadblocks in the caspase 1 inflammasome for interleukin-1β secretion and disease activity. Arthritis & Rheumatism 56:9, 2817-2822
CrossRef235
Michael F. McDermott, Jürg Tschopp. (2007) From inflammasomes to fevers, crystals and hypertension: how basic research explains inflammatory diseases. Trends in Molecular Medicine 13:9, 381-388
CrossRef236
I. A. Yang, J. W. Holloway. (2007) Asthma: advancing gene?environment studies. Clinical & Experimental Allergy 37:9, 1264-1266
CrossRef237
(2007) Interleukin-1–Receptor Antagonist in Type 2 Diabetes Mellitus. New England Journal of Medicine 357:3, 302-303
Full Text238
Rother, Kristina I., . (2007) Diabetes Treatment — Bridging the Divide. New England Journal of Medicine 356:15, 1499-1501
Full Text239
Charles A. Dinarello. (2007) A Signal for the Caspase-1 Inflammasome Free of TLR. Immunity 26:4, 383-385
CrossRef
- Letters
