Disruption of IRS-2 causes type 2 diabetes in mice
| Autor: | Yitao Zhang, Julio Sanchez Gutierrez, Sebastian Pons, Morris F. White, Dominic J. Withers, Stephen F. Previs, Gerald I. Shulman, Susan Bonner-Weir, Dolores Bernal, Heather H. Towery, Jian-Ming Ren, Deborah J. Burks |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Insulin Receptor Substrate Proteins medicine.medical_treatment Type 2 diabetes Biology Islets of Langerhans Mice Phosphatidylinositol 3-Kinases Insulin resistance Insulin Receptor Substrate 4 Internal medicine Diabetes mellitus medicine Animals Humans Insulin Glucose homeostasis Cloning Molecular Phosphorylation Muscle Skeletal Recombination Genetic Multidisciplinary Intracellular Signaling Peptides and Proteins Phosphoproteins medicine.disease Receptor Insulin IRS2 Mice Inbred C57BL Endocrinology Diabetes Mellitus Type 2 Liver Gene Targeting Female Insulin Resistance Signal Transduction |
| Zdroj: | ResearcherID |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/36116 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|