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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Oliveira, Joana Moitinho Rebuffat, Sandra A. Gasa, Rosa Gomis, Ramon |
| Description | Country affiliation: Spain Author Affiliation: Oliveira JM ( a Diabetes and Obesity Research Laboratory, Institut d'Investigations Biomediques August Pi i Sunyer, Centre Esther Koplowitz, C/Rosselló, 149-153 08036 Barcelona, Spain.) |
| Abstract | Insulin receptor substrate 2 (IRS2) is a widely expressed protein that regulates crucial biological processes including glucose metabolism, protein synthesis, and cell survival. IRS2 is part of the insulin - insulin-like growth factor (IGF) signaling pathway and mediates the activation of the phosphotidylinositol 3-kinase (PI3K)-Akt and the Ras-mitogen-activated protein kinase (MAPK) cascades in insulin target tissues and in the pancreas. The best evidence of this is that systemic elimination of the Irs2 in mice (Irs2(-/-)) recapitulates the pathogenesis of type 2 diabetes (T2D), in that diabetes arises as a consequence of combined insulin resistance and beta-cell failure. Indeed, work using this knockout mouse has confirmed the importance of IRS2 in the control of glucose homeostasis and especially in the survival and function of pancreatic beta-cells. These studies have shown that IRS2 is critically required for beta-cell compensation in conditions of increased insulin demand. Importantly, islets isolated from T2D patients exhibit reduced IRS2 expression, which supports the likely contribution of altered IRS2-dependent signaling to beta-cell failure in human T2D. For all these reasons, the Irs2(-/-) mouse has been and will be essential for elucidating the inter-relationship between beta-cell function and insulin resistance, as well as to delineate therapeutic strategies to protect beta-cells during T2D progression. |
| File Format | HTM / HTML |
| ISSN | 00084212 |
| e-ISSN | 12057541 |
| Journal | Canadian Journal of Physiology and Pharmacology |
| Issue Number | 8 |
| Volume Number | 92 |
| Language | English |
| Publisher | Canadian Science Publishing |
| Publisher Date | 2014-08-01 |
| Publisher Place | Canada |
| Access Restriction | Open |
| Subject Keyword | Discipline Physiology Discipline Pharmacology Diabetes Mellitus, Type 2 Metabolism Insulin Receptor Substrate Proteins Genetics Pancreas Animals Pathology Prevention & Control Disease Models, Animal Insulin Resistance Mice Mice, Knockout Organ Specificity Signal Transduction Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Pharmacology |
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