Current views on the mechanism of action of thiazolidinedione insulin sensitizers.
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.
Goldstein
B J
BJ
Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA. Barry.Goldstein@mail.tju.edu
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles