MafA is a key regulator of glucose-stimulated insulin secretion.
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.
Zhang
Chuan
C
Institute of Basic Medical Sciences and Laboratory Animal Resource Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Moriguchi
Takashi
T
Kajihara
Miwako
M
Esaki
Ritsuko
R
Harada
Ayako
A
Shimohata
Homare
H
Oishi
Hisashi
H
Hamada
Michito
M
Morito
Naoki
N
Hasegawa
Kazuteru
K
Kudo
Takashi
T
Engel
James Douglas
JD
Yamamoto
Masayuki
M
Takahashi
Satoru
S
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
D007328:Insulin; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D015534:Trans-Activators; D011189:Potassium Chloride; D001120:Arginine; D005947:Glucose