TY - JOUR
T1 - The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation
AU - Fukui, Kenji
AU - Yang, Qin
AU - Cao, Yang
AU - Takahashi, Noriko
AU - Hatakeyama, Hiroyasu
AU - Wang, Haiyan
AU - Wada, Jun
AU - Zhang, Yanling
AU - Marselli, Lorella
AU - Nammo, Takao
AU - Yoneda, Kazue
AU - Onishi, Mineki
AU - Higashiyama, Shigeki
AU - Matsuzawa, Yuji
AU - Gonzalez, Frank J.
AU - Weir, Gordon C.
AU - Kasai, Haruo
AU - Shimomura, Iichiro
AU - Miyagawa, Jun Ichiro
AU - Wollheim, Claes B.
AU - Yamagata, Kazuya
N1 - Funding Information:
We thank Ms. F. Katsube and Dr. A. Ihara for their valuable help with this study. We also thank Dr. R. Palmiter (University of Washington) for providing the RIP expression vector, Dr. J. Miyazaki (Osaka University) for the gift of MIN6 cells, and Dr. J.M. Zabolotny (Beth Israel Deaconess Medical Center) for critical reading of the manuscript. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The work of Drs. L.M. and G.C.W. was supported by grants from the National Institute of Health (NIH NCRR ICR U4Z RR 16606 and U19DK61251) and the Diabetes Research and Wellness Foundation. Drs C.B.W. and H.W. were supported by the Swiss National Science Foundation No 32-66907.01 and 32-66907.02.
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmet.2005.11.003
DO - 10.1016/j.cmet.2005.11.003
M3 - Article
C2 - 16330323
AN - SCOPUS:33644878503
VL - 2
SP - 373
EP - 384
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -
