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(Hypertension. 1997;29:691-699.)
© 1997 American Heart Association, Inc.
Articles |
Insulin and Insulin-Like Growth Factor in Normal and Pathological Cardiovascular Physiology
the Divisions of Endocrinology, Metabolism, and Hypertension, Wayne State University School of Medicine and VA Medical Center, Detroit, Mich.
Correspondence to James R. Sowers, MD, Director, Division of Endocrinology, Metabolism, and Hypertension, Wayne State University School of Medicine, 4201 St Antoine, UHC-4H, Detroit, MI 48201. E-mail sowers@oncgate.roc.wayne.edu
Key Words: insulin • insulin-like growth factor • endothelium • nitric oxide • vasculature
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Introduction |
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Over the past decade considerable data have been garnered suggesting that insulin, normally secreted only by the pancreas, and IGF-1, secreted by cells of the cardiovascular system, regulate normal cardiovascular physiological responses.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 101 102 Furthermore, there is emerging evidence that abnormal actions of these factors may contribute to disease states such as hypertension and atherosclerosis.38 39 This review presents the current understanding of mechanisms of the hemodynamic, metabolic, and growth effects of insulin and IGF-1 exerted on cardiovascular tissue under both normal and pathological conditions.
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Hemodynamic Actions of Insulin and IGF-1 |
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Insulin and IGF-1 have specific and physiological vascular actions in humans and experimentally derived animals and cause an increase in SMBF and a decrease in vascular resistance.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Studies by several investigative groups29 30 31 32 33 34 35 40 have shown that insulin increases SMBF in a dose-dependent fashion, with an ED50 for insulin of approximately 35 to 40 µU/mL in lean insulin-sensitive persons.40 In experimental animals, insulin has differential effects in different vascular beds, exerting vasodilatory effects on the femoral, aortic, coronary, and tail vasculature and vasoconstrictor effects in mesenteric arteries.2 3 14 15 16 99 100 101 102 There are also differential effects of insulin in the renal vascular bed, exerting a constricting effect on afferent arterioles and efferent arteriole vasodilation.101 Even gender differences in vascular responses to insulin have been reported.102 IGF-1 has effects on the regulation of vascular tone that are similar to those of insulin, with regional differences in vascular responses.31 36 38 39 103 104 105 Unlike insulin, however, IGF-1 is produced in cardiovascular tissue,8 9 10 11 12 38 39 40 41 where it likely exerts autocrine/paracrine effects.
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Role of NO in the Vascular Effects of Insulin and IGF-1 |
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The endothelium-derived relaxing factor NO appears to be an important mediator of
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