| First Author | Riopel M | Year | 2011 |
| Journal | J Pathol | Volume | 224 |
| Issue | 1 | Pages | 45-55 |
| PubMed ID | 21381031 | Mgi Jnum | J:171249 |
| Mgi Id | MGI:4949038 | Doi | 10.1002/path.2849 |
| Citation | Riopel M, et al. (2011) Conditional beta1-integrin-deficient mice display impaired pancreatic beta cell function. J Pathol 224(1):45-55 |
| abstractText | beta1-Integrin, a critical regulator of beta cell survival and function, has been shown to protect against cell death and promote insulin expression and secretion in rat and human islet cells in vitro. The aim of the present study was to examine whether the knockout of beta1-integrin in collagen I-producing cells would have physiological and functional implications in pancreatic endocrine cells in vivo. Using adult mice with a conditional knockout of beta1-integrin in collagen I-producing cells, the effects of beta1-integrin deficiency on glucose metabolism and pancreatic endocrine cells were examined. Male beta1-integrin-deficient mice display impaired glucose tolerance, with a significant reduction in pancreatic insulin content (p < 0.01). Morphometric analysis revealed a significant reduction in beta cell mass (p < 0.001) in beta1-integrin-deficient mice, along with a significant decrease in beta cell proliferation, Pdx-1 and Nkx6.1 expression when compared with controls. Interestingly, these physiological and morphometric alterations in female beta1-integrin-deficient mice were less significant. Furthermore, beta1-integrin-deficient mice displayed decreased FAK (p < 0.05) and ERK1/2 (p < 0.001) phosphorylation, reduced cyclin D1 levels (p < 0.001) and increased caspase 3 cleavage (p < 0.01), while no changes in Akt phosphorylation were observed, indicating that the beta1-integrin signals through the FAK-MAPK-ERK pathway in vivo. Our results demonstrate that beta1-integrin is involved in the regulation of glucose metabolism and contributes to the maintenance of beta cell survival and function in vivo. Copyright (c) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
