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Insulin Resistance and Atherosclerosis

Cell Biology of Diabetes Laboratory (J.N., N.O., P.J.L.), Baker Heart Research Institute, Melbourne 3181, Australia; Monash University, Departments of Immunology (N.O., P.J.L.) and Medicine (A.M.D., P.J.L.), Central and Eastern Clinical School, Alfred Hospital, Melbourne 3181, Australia; and Alfred Baker Medical Unit (A.M.D., P.J.L.), The Heart Centre, Alfred Hospital, Melbourne 3181, Australia

Correspondence: Address all correspondence and requests for reprints to: A/Prof. Peter J. Little, Head, Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Courier address: 75 Commercial Road, Prahran, 3181 Melbourne, VIC, Australia; Postal address: St. Kilda Road Central, P.O. Box 6492, Melbourne, VIC 8008, Australia. E-mail: peter.little{at}baker.edu.au

The epidemic of obesity in the developed world over the last two decades is driving a large increase in type 2 diabetes and consequentially setting the scene for an impending wave of cardiovascular morbidity and mortality. It is only now being recognized that the major antecedent of type 2 diabetes, insulin resistance with its attendant syndrome, is the major underlying cause of the susceptibility to type 2 diabetes and cardiovascular disease.

In metabolic tissues, insulin signaling via the phosphatidylinositol-3-kinase pathway leads to glucose uptake so that in insulin resistance a state of hyperglycemia occurs; other factors such as dyslipidemia and hypertension also arise. In cardiovascular tissues there are two pathways of insulin receptor signaling, one that is predominant in metabolic tissues (mediated by phosphatidylinositol-3-kinase) and another being a growth factor-like pathway (mediated by MAPK); the down-regulation of the former and continued activity of the latter pathway leads to atherosclerosis.

This review addresses the metabolic consequences of the insulin resistance syndrome, its relationship with atherosclerosis, and the impact of insulin resistance on processes of atherosclerosis including insulin signaling in cells of the vasculature.

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