| First Author | Fukui K | Year | 2005 |
| Journal | Cell Metab | Volume | 2 |
| Issue | 6 | Pages | 373-84 |
| PubMed ID | 16330323 | Mgi Jnum | J:129668 |
| Mgi Id | MGI:3769959 | Doi | 10.1016/j.cmet.2005.11.003 |
| Citation | Fukui K, et al. (2005) The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. Cell Metab 2(6):373-84 |
| abstractText | 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. |
