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PMID: 15923615 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

MafA is a key regulator of glucose-stimulated insulin secretion.

Molecular and cellular biology ·Vol. 25 ·No. 12 ·2005-06-00 ·Pages 4969-76

Zhang C, Moriguchi T, Kajihara M, Esaki R, Harada A, Shimohata H, Oishi H, Hamada M, Morito N, Hasegawa K, Kudo T, Engel JD, Yamamoto M, Takahashi S

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 beta 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.

MeSH Terms
Animals Arginine/administration & dosage,metabolism Cells, Cultured Diabetes Mellitus/genetics Female Gene Expression Regulation Gene Targeting Glucose/administration & dosage,metabolism Glucose Tolerance Test Insulin/genetics,metabolism Insulin Secretion Islets of Langerhans/abnormalities,cytology,drug effects,metabolism Maf Transcription Factors, Large Male Mice Mice, Knockout Potassium Chloride/pharmacology Trans-Activators/genetics,metabolism Transcription, Genetic
Chemicals
Insulin Maf Transcription Factors, Large Mafa protein, mouse Trans-Activators Potassium Chloride Arginine Glucose
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Zhang Chuan
Institute of Basic Medical Sciences and Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Moriguchi Takashi
Kajihara Miwako
Esaki Ritsuko
Harada Ayako
Shimohata Homare
Oishi Hisashi
Hamada Michito
Morito Naoki
Hasegawa Kazuteru
Kudo Takashi
Engel James Douglas
Yamamoto Masayuki
Takahashi Satoru
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.12.4969-4976.2005
Published
2005-06-00
Pages
4969-76
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1140590
Subset
IM
Grants
NCI NIH HHS · R01 CA080088 · United States
NCI NIH HHS · R01 CA80088 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.12.4969-4976.2005 PMC Full Text View journal details
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