title: MafA is a key regulator of glucose-stimulated insulin secretion.
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.
authors.affiliation: Institute of Basic Medical Sciences and Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhang
authors.forename: Takashi
authors.initials: T
authors.lastname: Moriguchi
authors.forename: Miwako
authors.initials: M
authors.lastname: Kajihara
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Esaki
authors.forename: Ayako
authors.initials: A
authors.lastname: Harada
authors.forename: Homare
authors.initials: H
authors.lastname: Shimohata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Oishi
authors.forename: Michito
authors.initials: M
authors.lastname: Hamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Morito
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000378:metabolism; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000002:abnormalities / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051473:Maf Transcription Factors, Large; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011189:Potassium Chloride / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D007328:Insulin; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D015534:Trans-Activators; D011189:Potassium Chloride; D001120:Arginine; D005947:Glucose