FROMMICE TO MEN Insights into the Insulin Resistance Syndromes英文文献.pdfVIP

Annu. Rev. Physiol. 2006. 68:123–58 doi: 10.1146/annurev.physiol.68.040104.124723 c Copyright 2006 by Annual Reviews. All rights reserved First published online as a Review in Advance on October 24, 2005 FROM MICE TO MEN: Insights into the Insulin Resistance Syndromes Sudha B. Biddinger1,2 and C. Ronald Kahn1 1Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215; email: sudha.biddinger@, c.ronald.kahn@ 2Division of Endocrinology, Children’s Hospital, Boston, Massachusetts 02215 ■ Abstract The insulin resistance syndrome refers to a constellation of findings, including glucose intolerance, obesity, dyslipidemia, and hypertension, that promote the development of type 2 diabetes, cardiovascular disease, cancer, and other disorders. Defining the pathophysiological links between insulin resistance, the insulin resistance syndrome, and its sequelae is critical to understanding and treating these disorders. Over the past decade, two approaches have provided important insights into how changes in insulin signaling produce the spectrum of phenotypes associated with insulin resis- tance. First, studies using tissue-specific knockouts or tissue-specific reconstitution of the insulin receptor in vivo in mice have enabled us to deconstruct the insulin resistance syndromes by dissecting the contributions of different tissues to the insulin-resistant state. Second, in vivo and in vitro studies of the complex network of insulin signal- ing have provided insight into how insulin resistance