Molecular Mechanisms of Insulin Resistance That Impact Cardiovascular Biology
- From the Research Service of the Denver Veterans Affairs Medical Center, and the Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado
- Address correspondence and reprint requests to Dr. Boris Draznin, ACOS for R&D (151), Denver VAMC, 1055 Clermont St, Denver, CO 80220. E-mail: boris.draznin{at}med.va.gov
Abstract
Insulin resistance is concomitant with type 2 diabetes, obesity, hypertension, and other features of the metabolic syndrome. Because insulin resistance is associated with cardiovascular disease, both scientists and physicians have taken great interest in this disorder. Insulin resistance is associated with compensatory hyperinsulinemia, but individual contributions of either of these two conditions remain incompletely understood and a subject of intense investigation. One possibility is that in an attempt to overcome the inhibition within the metabolic insulin-signaling pathway, hyperinsulinemia may continue to stimulate the mitogenic insulin-signaling pathway, thus exerting its detrimental influence. Here we discuss some of the effects of insulin resistance and mechanisms of potentially detrimental influence of hyperinsulinemia in the presence of metabolic insulin resistance.
- ARB, angiotensin receptor blocker
- eNOS, endothelial nitric oxide synthase
- FTase, farnesyltransferase
- GGTase I, geranylgeranyltransferase I
- HOPE, Heart Outcomes Prevention Evaluation
- IRS, insulin receptor substrate
- MAP, mitogen-activated protein
- NF-κB, nuclear factor-κB
- PDGF, platelet-derived growth factor
- PI, phosphatidylinosital
- PPAR, peroxisome proliferator–activated receptor
- RAAS, renin-angiotensin-aldosterone system
- SM-actin, smooth muscle α-actin
- VSMC, vascular smooth muscle cell
Footnotes
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- Accepted July 26, 2004.
- Received June 1, 2004.
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