| First Author | Feng ZC | Year | 2012 |
| Journal | Diabetologia | Volume | 55 |
| Issue | 8 | Pages | 2214-25 |
| PubMed ID | 22581040 | Mgi Jnum | J:186442 |
| Mgi Id | MGI:5432317 | Doi | 10.1007/s00125-012-2566-5 |
| Citation | Feng ZC, et al. (2012) Critical role of c-Kit in beta cell function: increased insulin secretion and protection against diabetes in a mouse model. Diabetologia 55(8):2214-25 |
| abstractText | AIMS/HYPOTHESIS: The receptor tyrosine kinase, c-Kit, and its ligand, stem cell factor, control a variety of cellular processes, including pancreatic beta cell survival and differentiation as revealed in c-Kit ( Wv ) mice, which have a point mutation in the c-Kit allele leading to loss of kinase activity and develop diabetes. The present study further investigated the intrinsic role of c-Kit in beta cells, especially the underlying mechanisms that influence beta cell function. METHODS: We generated a novel transgenic mouse model with c-KIT overexpression specifically in beta cells (c-KitbetaTg) to further examine the physiological and functional roles of c-Kit in beta cells. Isolated islets from these mice were used to investigate the underlying molecular pathway of c-Kit in beta cells. We also characterised the ability of c-Kit to protect animals from high-fat-diet-induced diabetes, as well as to rescue c-Kit ( Wv ) mice from early onset of diabetes. RESULTS: c-KitbetaTg mice exhibited improved beta cell function, with significantly improved insulin secretion, and increased beta cell mass and proliferation in response to high-fat-diet-induced diabetes. c-KitbetaTg islets exhibited upregulation of: (1) insulin receptor and IRSs; (2) Akt and glycogen synthase kinase 3beta phosphorylation; and (3) transcription factors important for islet function. c-KIT overexpression in beta cells also rescued diabetes observed in c-Kit ( Wv ) mice. CONCLUSIONS/INTERPRETATION: These findings demonstrate that c-Kit plays a direct protective role in beta cells, by regulating glucose metabolism and beta cell function. c-Kit may therefore represent a novel target for treating diabetes. |
