Disruption of IRS-2 causes type 2 diabetes in mice.
Journal:
Nature 1998 FebAuthors:
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
Abstract
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 resista
...[more]nce 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.[less]
Mesh Headings:
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