Current views on the mechanism of action of thiazolidinedione insulin sensitizers

Abstract

Resistance to the action of insulin in its target tissues in a major predisposing factor for the development of type 2 diabetes and is also tightly associated with a common pattern of cardiovascular risk factors that characterize the "insulin resistance syndrome." The thiazolidinediones are a new class of drugs that act as insulin sensitizers with well-documented-efficacy in the control of hyperglycemia in patients with overt diabetes. A growing body of evidence also suggests that thiazolidinediones may preserve beta-cell function and protect cardiovascular and renal function in patients with type 2 diabetes. This review will summarize our current notions of the mechanism of action of thiazolidinediones, which appears to involve a fascinating interplay between the partitioning of triglyceride stores, circulating free fatty acids and insulin signaling pathways. A detailed understanding of the action of thiazolidinediones will provide new insights into the pathogenesis of insulin resistance, diabetes and some of the causes of increased cardiovascular mortality in these conditions.