PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function.
Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintenance of mature beta-cell function. PDX-1 expression is maintained in pancreatic precursor cells during pancreas development but becomes restricted to beta-cells in mature pancreas. In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. Furthermore, these transcription factors play an important role in induction of insulin-producing cells in various 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. 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.
Kaneto
Hideaki
H
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Osaka, Japan.
Miyatsuka
Takeshi
T
Kawamori
Dan
D
Yamamoto
Kaoru
K
Kato
Ken
K
Shiraiwa
Toshihiko
T
Katakami
Naoto
N
Yamasaki
Yoshimitsu
Y
Matsuhisa
Munehide
M
Matsuoka
Taka-Aki
TA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D051473:Maf Transcription Factors, Large / Q000502:physiology*; D051379:Mice; D051381:Rats; D015534:Trans-Activators / Q000502:physiology*
D018398:Homeodomain Proteins; D007328:Insulin; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose