Correspondence

Sympathetic-Nerve Activity before and after Resection of an Insulinoma

N Engl J Med 1996; 335:1240-1242October 17, 1996

Article

To the Editor:

The prevalence of hypertension is increased in patients with insulin resistance and hyperinsulinemia. This observation has led to the hypothesis that insulin causes hypertension, and insulin-induced stimulation of renal sodium reabsorption, vascular smooth-muscle growth, and sympathetic-nerve activity have been proposed as potential pathogenetic mechanisms.1 The proposal that sympathetic-nerve activity is a pathogenetic mechanism is based on the observations that short-term insulin infusions in lean subjects stimulate sympathetic-nerve activity and that obesity (a state characterized by hyperinsulinemia) is associated with sustained sympathetic activation.2,3 However, the sympathoexcitatory effects of sustained hyperinsulinemia cannot be established on the basis of such correlational and short-term–infusion studies.

Patients with insulinomas have hyperinsulinemia but little insulin resistance,1 and this situation provides an opportunity to examine the effects of sustained hyperinsulinemia on sympathetic-nerve activity. We recorded sympathetic-nerve activity2 before and after the removal of a benign insulinoma in a patient with a 24-month history of hypoglycemic symptoms. We also assessed the responses to other stimuli3 and the postoperative sympathetic effects of an acute elevation of the plasma insulin concentration to the preoperative level. Before surgery, despite plasma insulin concentrations that were roughly four times higher than normal, the rate of sympathetic-nerve activity in this patient was normal and similar to that after removal of the insulinoma (Figure 1Figure 1Recordings of Sympathetic-Nerve Activity and Corresponding Values for Plasma Insulin and Glucose Concentrations, Blood Pressure, and Heart Rate before and Seven Weeks after the Removal of an Insulinoma in a 20-Year-Old Man.). This finding was not related to a generalized impairment of sympathetic responsiveness (as evidenced by normal sympathetic-nerve responses to immersion of the hand in ice water and the Valsalva maneuver). The lack of sympathetic activation in this patient before surgery could have been related to the down-regulation of central insulin-sensitive receptors as a result of sustained hyperinsulinemia. After surgery, an acute elevation of the plasma insulin concentration to the preoperative level was associated with sympathetic activation, which is consistent with this hypothesis. These results indicate that one has to be cautious when drawing inferences about the sympathetic effects of chronic hyperinsulinemia on the basis of euglycemic–hyperinsulinemic clamp studies.

Obesity is associated with a greater-than-expected incidence of hypertension, and blood pressure decreases with weight loss.1 In contrast, among patients with insulinomas, the incidence of hypertension is not increased, and blood pressure does not decrease after the removal of the tumor.4 The finding that sympathetic-nerve activity was normal in a patient with an insulinoma and did not change after the removal of the tumor — whereas in obese persons, sympathetic activity is augmented2,3 and decreases with weight loss5 — may explain these clinical observations.

Urs Scherrer, M.D.
Reza Owlya, M.D.
Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland

Lionel Trueb, M.D.
Institute of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland

5 References

1. 1

   Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities -- the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996;334:374-381
   Full Text | Web of Science | Medline

2. 2

   Scherrer U, Randin D, Tappy L, Vollenweider P, Jequier E, Nicod P. Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994;89:2634-2640
   Web of Science | Medline

3. 3

   Vollenweider P, Randin D, Tappy L, Jequier E, Nicod P, Scherrer U. Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. J Clin Invest 1994;93:2365-2371
   CrossRef | Web of Science | Medline

4. 4

   Fujita N, Baba T, Tomiyama T, Kodama T, Kako N. Hyperinsulinaemia and blood pressure in patients with insulinoma. BMJ 1992;304:1157-1157
   CrossRef | Web of Science | Medline

5. 5

   Andersson B, Elam M, Wallin BG, Bjorntorp P, Andersson OK. Effect of energy-restricted diet on sympathetic muscle nerve activity in obese women. Hypertension 1991;18:783-789
   Web of Science | Medline

Citing Articles (8)

Citing Articles

1. 1

   J. A. N. Dorresteijn, F. L. J. Visseren, W. Spiering. (2011) Mechanisms linking obesity to hypertension. Obesity Reviewsno-no
   CrossRef

2. 2

   Kevin P. Davy, Jeb S. Orr. (2009) Sympathetic nervous system behavior in human obesity. Neuroscience & Biobehavioral Reviews 33:2, 116-124
   CrossRef

3. 3

   E. A. Francischetti, V. A. Genelhu. (2007) Obesity-hypertension: an ongoing pandemic. International Journal of Clinical Practice 61:2, 269-280
   CrossRef

4. 4

   Kevin P. Davy. (2004) The global epidemic of obesity: Are we becoming more sympathetic?. Current Hypertension Reports 6:3, 241-246
   CrossRef

5. 5

   Norika Tamaya-Mori, Kazumasa Uemura, Shin Tanaka, Akihisa Iguchi. (2003) Aging accelerates dietary lard-induced increase in blood pressure in rats. Experimental Gerontology 38:8, 905-910
   CrossRef

6. 6

   Claudio Sartori, Urs Scherrer. (1999) Insulin, nitric oxide and the sympathetic nervous system. Journal of Hypertension 17:11, 1517-1525
   CrossRef

7. 7

   Michel Galinier, Joëlle Fourcade, Serge Boveda, Nicolas Ley, Sophie Solera, Marie Laure Solera, Octavian Pîrvu, Pierre Massabuau, Philippe Cabrol, Jean Marie Fauvel, Pierre Valdiguie, Jean Paul Bounhoure. (1999) Relationships of Chronic Hyperinsulinemia, Heart Rate Variability, and Circadian Variation of Blood Pressure in Obese Hypertensive Subjects. Annals of Noninvasive Electrocardiology 4:3, 316-324
   CrossRef

8. 8

   Gees J.J. Tack, Jacques W.M. Lenders, David S. Goldstein, Jos A. Lutterman, Paul Smits, Theo Thien. (1998) Haemodynamic actions of insulin. Current Opinion in Nephrology and Hypertension 7:1, 99-106
   CrossRef