Abstract
Insulin exerts effects on the vasculature that (a) may play a role in the regulation of blood pressure; and (b) by boosting its own delivery to target tissues, also have been proposed to play an integral part in its main action, the promotion of glucose disposal. To study the role of nitric oxide (NO) in the mediation of insulin's effects on the peripheral vasculature, NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived NO, was infused into the brachial arteries of healthy volunteers both before, and at the end of a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp. L-NMMA (but not norepinephrine, an NO-independent vasoconstrictor) caused larger reductions in forearm blood flow during hyperinsulinemia than at baseline. Moreover, L-NMMA prevented insulin-induced vasodilation throughout the clamp. Prevention of vasodilation by L-NMMA led to significant increases in arterial pressure during insulin/glucose infusion but did not alter glucose uptake. These findings indicate that insulin's vasodilatory effects are mediated by stimulation of NO release, and that they play a role in the regulation of arterial pressure during physiologic hyperinsulinemia. Abnormalities in insulin-induced NO release could contribute to altered vascular function and hypertension in insulin-resistant states.
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Selected References
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- 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]
- Baron A. D. Cardiovascular actions of insulin in humans. Implications for insulin sensitivity and vascular tone. Baillieres Clin Endocrinol Metab. 1993 Oct;7(4):961–987. doi: 10.1016/s0950-351x(05)80241-1. [DOI] [PubMed] [Google Scholar]
- Calver A., Collier J., Vallance P. Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes. J Clin Invest. 1992 Dec;90(6):2548–2554. doi: 10.1172/JCI116149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feldman R. D., Bierbrier G. S. Insulin-mediated vasodilation: impairment with increased blood pressure and body mass. Lancet. 1993 Sep 18;342(8873):707–709. doi: 10.1016/0140-6736(93)91708-t. [DOI] [PubMed] [Google Scholar]
- GINSBURG J., PATON A. Effects of insulin after adrenalectomy. Lancet. 1956 Sep 8;271(6941):491–494. doi: 10.1016/s0140-6736(56)91973-0. [DOI] [PubMed] [Google Scholar]
- GREENFIELD A. D., PATTERSON G. C. Reactions of the blood vessels of the human forearm to increases in transmural pressure. J Physiol. 1954 Sep 28;125(3):508–524. doi: 10.1113/jphysiol.1954.sp005177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Modan M., Halkin H., Almog S., Lusky A., Eshkol A., Shefi M., Shitrit A., Fuchs Z. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest. 1985 Mar;75(3):809–817. doi: 10.1172/JCI111776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Randin D., Vollenweider P., Tappy L., Jéquier E., Nicod P., Scherrer U. Effects of adrenergic and cholinergic blockade on insulin-induced stimulation of calf blood flow in humans. Am J Physiol. 1994 Mar;266(3 Pt 2):R809–R816. doi: 10.1152/ajpregu.1994.266.3.R809. [DOI] [PubMed] [Google Scholar]
- Saenz de Tejada I., Goldstein I., Azadzoi K., Krane R. J., Cohen R. A. Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med. 1989 Apr 20;320(16):1025–1030. doi: 10.1056/NEJM198904203201601. [DOI] [PubMed] [Google Scholar]
- 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]
- Tagawa T., Imaizumi T., Endo T., Shiramoto M., Hirooka Y., Ando S., Takeshita A. Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels. J Clin Invest. 1993 Sep;92(3):1483–1490. doi: 10.1172/JCI116726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vallance P., Collier J., Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989 Oct 28;2(8670):997–1000. doi: 10.1016/s0140-6736(89)91013-1. [DOI] [PubMed] [Google Scholar]
- Vollenweider P., Randin D., Tappy L., Jéquier E., Nicod P., Scherrer U. Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. J Clin Invest. 1994 Jun;93(6):2365–2371. doi: 10.1172/JCI117242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Wang Y. X., Poon C. I., Pang C. C. Vascular pharmacodynamics of NG-nitro-L-arginine methyl ester in vitro and in vivo. J Pharmacol Exp Ther. 1993 Dec;267(3):1091–1099. [PubMed] [Google Scholar]
- 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]