Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jun;93(6):2365–2371. doi: 10.1172/JCI117242

Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans.

P Vollenweider 1, D Randin 1, L Tappy 1, E Jéquier 1, P Nicod 1, U Scherrer 1
PMCID: PMC294442  PMID: 8200969

Abstract

The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic activity may play a role in the etiology and/or complications of obesity. In lean subjects, insulin evokes sympathetic activation and vasodilation in skeletal muscle. In obese subjects such vasodilation is impaired and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skeletal muscle to hyperinsulinemia, we simultaneously measured muscle sympathetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight lean and eight obese subjects. The major findings of this study are twofold: obese subjects had a 2.2 times higher fasting rate of MSNA, and euglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vasodilatory and sympathoexcitatory effect in obese subjects. In contrast, two non-insulin-sympathetic stimuli evoked comparably large increases in MSNA in lean and obese subjects. We conclude that insulin resistance in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiological hyperinsulinemia in skeletal muscle tissue.

Full text

PDF
2369

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acheson K., Jéquier E., Wahren J. Influence of beta-adrenergic blockade on glucose-induced thermogenesis in man. J Clin Invest. 1983 Sep;72(3):981–986. doi: 10.1172/JCI111070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson E. A., Hoffman R. P., Balon T. W., Sinkey C. A., Mark A. L. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 1991 Jun;87(6):2246–2252. doi: 10.1172/JCI115260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baron A. D., Brechtel G. Insulin differentially regulates systemic and skeletal muscle vascular resistance. Am J Physiol. 1993 Jul;265(1 Pt 1):E61–E67. doi: 10.1152/ajpendo.1993.265.1.E61. [DOI] [PubMed] [Google Scholar]
  4. Bray G. A., York D. A., Fisler J. S. Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system. Vitam Horm. 1989;45:1–125. doi: 10.1016/s0083-6729(08)60393-3. [DOI] [PubMed] [Google Scholar]
  5. Ciaraldi T. P., Kolterman O. G., Olefsky J. M. Mechanism of the postreceptor defect in insulin action in human obesity. Decrease in glucose transport system activity. J Clin Invest. 1981 Oct;68(4):875–880. doi: 10.1172/JCI110342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
  7. Delius W., Hagbarth K. E., Hongell A., Wallin B. G. Manoeuvres affecting sympathetic outflow in human muscle nerves. Acta Physiol Scand. 1972 Jan;84(1):82–94. doi: 10.1111/j.1748-1716.1972.tb05157.x. [DOI] [PubMed] [Google Scholar]
  8. Dohm G. L., Tapscott E. B., Pories W. J., Dabbs D. J., Flickinger E. G., Meelheim D., Fushiki T., Atkinson S. M., Elton C. W., Caro J. F. An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. J Clin Invest. 1988 Aug;82(2):486–494. doi: 10.1172/JCI113622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GREENFIELD A. D., WHITNEY R. J., MOWBRAY J. F. Methods for the investigation of peripheral blood flow. Br Med Bull. 1963 May;19:101–109. doi: 10.1093/oxfordjournals.bmb.a070026. [DOI] [PubMed] [Google Scholar]
  10. Hallman H., Farnebo L. O., Hamberger B., Johnsson G. A sensitive method for the determination of plasma catecholamines using liquid chromatography with electrochemical detection. Life Sci. 1978 Sep 11;23(10):1049–1052. doi: 10.1016/0024-3205(78)90665-3. [DOI] [PubMed] [Google Scholar]
  11. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  12. Holt S., York D. A., Fitzsimons J. T. The effects of corticosterone, cold exposure and overfeeding with sucrose on brown adipose tissue of obese Zucker rats (fa/fa). Biochem J. 1983 Jul 15;214(1):215–223. doi: 10.1042/bj2140215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jansson P. A., Fowelin J. P., von Schenck H. P., Smith U. P., Lönnroth P. N. Measurement by microdialysis of the insulin concentration in subcutaneous interstitial fluid. Importance of the endothelial barrier for insulin. Diabetes. 1993 Oct;42(10):1469–1473. doi: 10.2337/diab.42.10.1469. [DOI] [PubMed] [Google Scholar]
  14. Joyner M. J., Lennon R. L., Wedel D. J., Rose S. H., Shepherd J. T. Blood flow to contracting human muscles: influence of increased sympathetic activity. J Appl Physiol (1985) 1990 Apr;68(4):1453–1457. doi: 10.1152/jappl.1990.68.4.1453. [DOI] [PubMed] [Google Scholar]
  15. Kolterman O. G., Insel J., Saekow M., Olefsky J. M. Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. J Clin Invest. 1980 Jun;65(6):1272–1284. doi: 10.1172/JCI109790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laakso M., Edelman S. V., Brechtel G., Baron A. D. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest. 1990 Jun;85(6):1844–1852. doi: 10.1172/JCI114644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Laakso M., Edelman S. V., Brechtel G., Baron A. D. Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM. Diabetes. 1992 Sep;41(9):1076–1083. doi: 10.2337/diab.41.9.1076. [DOI] [PubMed] [Google Scholar]
  18. Lembo G., Napoli R., Capaldo B., Rendina V., Iaccarino G., Volpe M., Trimarco B., Saccà L. Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. J Clin Invest. 1992 Jul;90(1):24–29. doi: 10.1172/JCI115842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Modan M., Halkin H. Hyperinsulinemia or increased sympathetic drive as links for obesity and hypertension. Diabetes Care. 1991 Jun;14(6):470–487. doi: 10.2337/diacare.14.6.470. [DOI] [PubMed] [Google Scholar]
  20. Olefsky J. M. LIlly lecture 1980. Insulin resistance and insulin action. An in vitro and in vivo perspective. Diabetes. 1981 Feb;30(2):148–162. doi: 10.2337/diab.30.2.148. [DOI] [PubMed] [Google Scholar]
  21. Parati G., Casadei R., Groppelli A., Di Rienzo M., Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension. 1989 Jun;13(6 Pt 1):647–655. doi: 10.1161/01.hyp.13.6.647. [DOI] [PubMed] [Google Scholar]
  22. Reaven G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595–1607. doi: 10.2337/diab.37.12.1595. [DOI] [PubMed] [Google Scholar]
  23. Scherrer U., Vollenweider P., Randin D., Jéquier E., Nicod P., Tappy L. Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans. Circulation. 1993 Aug;88(2):388–394. doi: 10.1161/01.cir.88.2.388. [DOI] [PubMed] [Google Scholar]
  24. Spraul M., Ravussin E., Fontvieille A. M., Rising R., Larson D. E., Anderson E. A. Reduced sympathetic nervous activity. A potential mechanism predisposing to body weight gain. J Clin Invest. 1993 Oct;92(4):1730–1735. doi: 10.1172/JCI116760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Vallbo A. B., Hagbarth K. E., Torebjörk H. E., Wallin B. G. Somatosensory, proprioceptive, and sympathetic activity in human peripheral nerves. Physiol Rev. 1979 Oct;59(4):919–957. doi: 10.1152/physrev.1979.59.4.919. [DOI] [PubMed] [Google Scholar]
  26. Victor R. G., Leimbach W. N., Jr, Seals D. R., Wallin B. G., Mark A. L. Effects of the cold pressor test on muscle sympathetic nerve activity in humans. Hypertension. 1987 May;9(5):429–436. doi: 10.1161/01.hyp.9.5.429. [DOI] [PubMed] [Google Scholar]
  27. Vollenweider P., Tappy L., Randin D., Schneiter P., Jéquier E., Nicod P., Scherrer U. Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest. 1993 Jul;92(1):147–154. doi: 10.1172/JCI116542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yang Y. J., Hope I. D., Ader M., Bergman R. N. Insulin transport across capillaries is rate limiting for insulin action in dogs. J Clin Invest. 1989 Nov;84(5):1620–1628. doi: 10.1172/JCI114339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Young J. B., Landsberg L. Diminished sympathetic nervous system activity in genetically obese (ob/ob) mouse. Am J Physiol. 1983 Aug;245(2):E148–E154. doi: 10.1152/ajpendo.1983.245.2.E148. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES