| First Author | Chen Z | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 2 | Pages | 585-95 |
| PubMed ID | 24150605 | Mgi Jnum | J:209019 |
| Mgi Id | MGI:5565557 | Doi | 10.2337/db13-0666 |
| Citation | Chen Z, et al. (2014) SH2B1 in beta-cells regulates glucose metabolism by promoting beta-cell survival and islet expansion. Diabetes 63(2):585-95 |
| abstractText | IGF-1 and insulin promote beta-cell expansion by inhibiting beta-cell death and stimulating beta-cell proliferation, and the phosphatidylinositol (PI) 3-kinase/Akt pathway mediates insulin and IGF-1 action. Impaired beta-cell expansion is a risk factor for type 2 diabetes. Here, we identified SH2B1, which is highly expressed in beta-cells, as a novel regulator of beta-cell expansion. Silencing of SH2B1 in INS-1 832/13 beta-cells attenuated insulin- and IGF-1-stimulated activation of the PI 3-kinase/Akt pathway and increased streptozotocin (STZ)-induced apoptosis; conversely, overexpression of SH2B1 had the opposite effects. Activation of the PI 3-kinase/Akt pathway in beta-cells was impaired in pancreas-specific SH2B1 knockout (PKO) mice fed a high-fat diet (HFD). HFD-fed PKO mice also had increased beta-cell apoptosis, decreased beta-cell proliferation, decreased beta-cell mass, decreased pancreatic insulin content, impaired insulin secretion, and exacerbated glucose intolerance. Furthermore, PKO mice were more susceptible to STZ-induced beta-cell destruction, insulin deficiency, and hyperglycemia. These data indicate that SH2B1 in beta-cells is an important prosurvival and proproliferative protein and promotes compensatory beta-cell expansion in the insulin-resistant state and in response to beta-cell stress. |
