A crucial role of MafA as a novel therapeutic target for diabetes.
MafA, a recently isolated pancreatic beta-cell-specific transcription factor, is a potent activator of insulin gene transcription. In this study, we show that MafA overexpression, together with PDX-1 (pancreatic and duodenal homeobox factor-1) and NeuroD, markedly increases insulin gene expression in the liver. Consequently, substantial amounts of insulin protein were induced by such combination. Furthermore, in streptozotocin-induced diabetic mice, MafA overexpression in the liver, together with PDX-1 and NeuroD, dramatically ameliorated glucose tolerance, while combination of PDX-1 and NeuroD was much less effective. These results suggest a crucial role of MafA as a novel therapeutic target for diabetes.
Kaneto
Hideaki
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@medone.med.osaka-u.ac.jp
Matsuoka
Taka-aki
TA
Nakatani
Yoshihisa
Y
Miyatsuka
Takeshi
T
Matsuhisa
Munehide
M
Hori
Masatsugu
M
Yamasaki
Yoshimitsu
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003920:Diabetes Mellitus / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051473:Maf Transcription Factors, Large; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005947:Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D008156:Luciferases; D051473:Maf Transcription Factors, Large; D013311:Streptozocin; D015534:Trans-Activators; C485159:MAFA protein, human; C093970:NEUROD1 protein, human; C501008:Neurod1 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein