Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1α 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-1α in pancreatic β cells. Expression of collectrin was decreased in the islets of HNF-1α (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the β cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca2+ 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.
|Autori:||Fukui K;Yang Q;Cao Y;Takahashi N;Hatakeyama H;Wang H;Wada J;Zhang Y;Marselli L;Nammo T;Yoneda K;Onishi M;Higashiyama S;Matsuzawa Y;Gonzalez FJ;Weir GC;Kasai H;Shimomura I;Miyagawa J;Wollheim CB;Yamagata K|
|Titolo:||The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation.|
|Anno del prodotto:||2005|
|Digital Object Identifier (DOI):||10.1016/j.cmet.2005.11.003|
|Appare nelle tipologie:||1.1 Articolo in rivista|