2. Academic Validation
  3. The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation

The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation

  • Cell Metab. 2005 Dec;2(6):373-84. doi: 10.1016/j.cmet.2005.11.003.
Kenji Fukui 1,  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
Affiliations

Affiliation

  • 1 Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita Osaka 565-0871, Japan.
PMID: 16330323 DOI: 10.1016/j.cmet.2005.11.003
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.

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