| Literature DB >> 16330323 |
Kenji Fukui1, Qin Yang, Yang Cao, Noriko Takahashi, Hiroyasu Hatakeyama, Haiyan Wang, Jun Wada, Yanling Zhang, Lorella Marselli, Takao Nammo, Kazue Yoneda, Mineki Onishi, Shigeki Higashiyama, Yuji Matsuzawa, Frank J Gonzalez, Gordon C Weir, Haruo Kasai, Iichiro Shimomura, Jun-ichiro Miyagawa, Claes B Wollheim, Kazuya Yamagata.
Abstract
Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis.Entities:
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Year: 2005 PMID： 16330323 DOI： 10.1016/j.cmet.2005.11.003
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287