PDX-1 functions as a master factor in the pancreas.
Various pancreatic transcription factors are involved in pancreas development and beta-cell differentiation. Among them, pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development and beta-cell differentiation, and maintaining mature beta-cell function. MafA is a recently isolated beta-cell-specific transcription factor and functions as a potent activator of insulin gene transcription. These pancreatic transcription factors also play a crucial role in inducing surrogate beta-cells from non-beta-cells and thus could be therapeutic targets for diabetes. On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. Thus, it is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes.
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@medone.med.osaka-u.ac.jp
Hideaki
H
Kaneto
Taka-aki
TA
Matsuoka
Takeshi
T
Miyatsuka
Dan
D
Kawamori
Naoto
N
Katakami
Yoshimitsu
Y
Yamasaki
Munehide
M
Matsuhisa
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D010179:Pancreas / Q000166:cytology / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007328:Insulin; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein