| First Author | He XQ | Year | 2020 |
| Journal | Mol Cell Endocrinol | Volume | 518 |
| Pages | 111004 | PubMed ID | 32871224 |
| Mgi Jnum | J:300686 | Mgi Id | MGI:6490223 |
| Doi | 10.1016/j.mce.2020.111004 | Citation | He XQ, et al. (2020) Specific deletion of CDC42 in pancreatic beta cells attenuates glucose-induced insulin expression and secretion in mice. Mol Cell Endocrinol 518:111004 |
| abstractText | Insulin is a key hormone for maintaining glucose homeostasis in organisms. In general, deficiency of insulin synthesis and secretion results in type I diabetes, whereas insulin resistance leads to type 2 diabetes. Cell division cycle 42 (CDC42), a member of Rho GTPases family, has been shown as an essential regulator in the second phase of glucose-induced insulin secretion in pancreatic islets beta cells in vitro. However, the effect of CDC42 on insulin expression has not been explored. Here we reported that the glucose-induced insulin expression and secretion were significantly inhibited in mice lacking CDC42 gene in pancreatic beta cells (Rip-CDC42cKO) in vivo and in vitro. Deletion of CDC42 gene in pancreatic beta cells did not affect survival or reproduction in mice. However, the Rip-CDC42cKO mice showed the systemic glucose intolerance and the decrease of glucose-induced insulin secretion without apparent alterations of peripheral tissues insulin sensitivity and the morphology of islets. Furthermore, we demonstrated that deletion of CDC42 gene in pancreatic beta cells significantly attenuated the insulin expression through inhibiting the ERK1/2-NeuroD1 signaling pathway. Taken together, our study presents novel evidence that CDC42 is an important modulator in glucose-induced insulin expression as well as insulin secretion in pancreatic beta cells. |
