| First Author | Ren D | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 10 | Pages | 3378-87 |
| PubMed ID | 24760140 | Mgi Jnum | J:229863 |
| Mgi Id | MGI:5754694 | Doi | 10.2337/db13-1814 |
| Citation | Ren D, et al. (2014) BH3-only molecule Bim mediates beta-cell death in IRS2 deficiency. Diabetes 63(10):3378-87 |
| abstractText | Irs2-deficient mice develop type 2-like diabetes due to a reduction in beta-cell mass and a failure of pancreatic islets to undergo compensatory hyperplasia in response to insulin resistance. In order to define the molecular mechanisms, we knocked down Irs2 gene expression in mouse MIN6 insulinoma cells. Insulin receptor substrate 2 (IRS2) suppression induced apoptotic cell death, which was associated with an increase in expression of the BH3-only molecule Bim. Knockdown (KD) of Bim reduced apoptotic beta-cell death induced by IRS2 suppression. In Irs2-deficient mice, Bim ablation restored beta-cell mass, decreased the number of TUNEL-positive cells, and restored normal glucose tolerance after glucose challenge. FoxO1 mediates Bim upregulation induced by IRS2 suppression, and FoxO1 KD partially inhibits beta-cell death induced by IRS2 suppression. These results suggest that Bim plays an important role in mediating the increase in beta-cell apoptosis and the reduction in beta-cell mass that occurs in IRS2-deficient diabetes. |
