Abstract：
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-KitβTg) 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-KitβTg 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-KitβTg islets exhibited upregulation of: (1) insulin receptor and IRSs; (2) Akt and glycogen synthase kinase 3β 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.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Feng ZC,Li J,Turco BA,Riopel M,Yee SP,Wang Rdoi
10.1007/s00125-012-2566-5subject
Has Abstractpub_date
2012-08-01 00:00:00pages
2214-25issue
8eissn
0012-186Xissn
1432-0428journal_volume
55pub_type
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