MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion
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Published:2005-06-15
Issue:12
Volume:25
Page:4969-4976
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ISSN:0270-7306
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Container-title:Molecular and Cellular Biology
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language:en
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Short-container-title:Mol Cell Biol
Author:
Zhang Chuan1, Moriguchi Takashi12, Kajihara Miwako1, Esaki Ritsuko1, Harada Ayako1, Shimohata Homare1, Oishi Hisashi1, Hamada Michito1, Morito Naoki1, Hasegawa Kazuteru1, Kudo Takashi1, Engel James Douglas2, Yamamoto Masayuki3, Takahashi Satoru1
Affiliation:
1. Institute of Basic Medical Sciences and Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan 2. University of Michigan Medical School, Ann Arbor, Michigan 48109-0616 3. Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan
Abstract
ABSTRACT
MafA is a transcription factor that binds to the promoter in the insulin gene and has been postulated to regulate insulin transcription in response to serum glucose levels, but there is no current in vivo evidence to support this hypothesis. To analyze the role of MafA in insulin transcription and glucose homeostasis in vivo, we generated MafA-deficient mice. Here we report that
MafA
mutant mice display intolerance to glucose and develop diabetes mellitus. Detailed analyses revealed that glucose-, arginine-, or KCl-stimulated insulin secretion from pancreatic β cells is severely impaired, although insulin content per se is not significantly affected. MafA-deficient mice also display age-dependent pancreatic islet abnormalities. Further analysis revealed that insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 transcripts are diminished in MafA-deficient mice. These results show that MafA is a key regulator of glucose-stimulated insulin secretion in vivo.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference33 articles.
1. Ahlgren, U., J. Jonsson, L. Jonsson, K. Simu, and H. Edlund. 1998. β-Cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes. Genes Dev. 12 : 1763-1768. 2. Benkhelifa, S., S. Provot, O. Lecoq, C. Pouponnot, G. Calothy, and M. P. Felder-Schmittbuhl. 1998. mafA, a novel member of the maf proto-oncogene family, displays developmental regulation and mitogenic capacity in avian neuroretina cells. Oncogene 17 : 247-254. 3. Brissova, M., M. Shiota, W. E. Nicholson, M. Gannon, S. M. Knobel, D. W. Piston, C. V. Wright, and A. C. Powers. 2002. Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. J. Biol. Chem. 277 : 11225-11232. 4. Furuta, H., Y. Horikawa, N. Iwasaki, M. Hara, L. Sussel, M. M. Le Beau, E. M. Davis, M. Ogata, Y. Iwamoto, M. S. German, and G. I. Bell. 1998. β-Cell transcription factors and diabetes: mutations in the coding region of the BETA2/NeuroD1 (NEUROD1) and Nkx2.2 (NKX2B) genes are not associated with maturity-onset diabetes of the young in Japanese. Diabetes 47 : 1356-1358. 5. Guillam, M. T., E. Hummler, E. Schaerer, J. I. Yeh, M. J. Birnbaum, F. Beermann, A. Schmidt, N. Deriaz, and B. Thorens. 1997. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat. Genet. 17 : 327-330.
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