Disruption of IRS-2 causes type 2 diabetes in mice.

Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF
Nature. 1998 391 (6670): 900-4

PMID: 9495343 · DOI:10.1038/36116

Human type 2 diabetes is characterized by defects in both insulin action and insulin secretion. It has been difficult to identify a single molecular abnormality underlying these features. Insulin-receptor substrates (IRS proteins) may be involved in type 2 diabetes: they mediate pleiotropic signals initiated by receptors for insulin and other cytokines. Disruption of IRS-1 in mice retards growth, but diabetes does not develop because insulin secretion increases to compensate for the mild resistance to insulin. Here we show that disruption of IRS-2 impairs both peripheral insulin signalling and pancreatic beta-cell function. IRS-2-deficient mice show progressive deterioration of glucose homeostasis because of insulin resistance in the liver and skeletal muscle and a lack of beta-cell compensation for this insulin resistance. Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes.

MeSH Terms (23)

Animals Blood Glucose Cloning, Molecular Diabetes Mellitus, Type 2 Female Gene Targeting Humans Insulin Insulin Receptor Substrate Proteins Insulin Resistance Intracellular Signaling Peptides and Proteins Islets of Langerhans Liver Male Mice Mice, Inbred C57BL Muscle, Skeletal Phosphatidylinositol 3-Kinases Phosphoproteins Phosphorylation Receptor, Insulin Recombination, Genetic Signal Transduction

Connections (1)

This publication is referenced by other Labnodes entities:

Links