Crucial role of PDX-1 in pancreas development, beta-cell differentiation, and induction of surrogate beta-cells.
Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintaining mature beta-cell function. At an early stage of embryonic development, PDX-1 is initially expressed in the gut region when the foregut endoderm becomes committed to common pancreatic precursor cells. During pancreas development, PDX-1 expression is maintained in precursor cells, and later it becomes restricted to beta-cells. In mature beta-cells, PDX-1 transactivates the insulin gene 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. During pancreas development, MafA expression is first detected at the beginning of the principal phase of insulin-producing cell production. Furthermore, these transcription factors play a crucial role in inducing surrogate beta-cells from non-beta-cells and thus could be therapeutic targets for diabetes.
Kaneto
Hideaki
H
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
Miyatsuka
Takeshi
T
Shiraiwa
Toshihiko
T
Yamamoto
Kaoru
K
Kato
Ken
K
Fujitani
Yoshio
Y
Matsuoka
Taka-aki
TA
D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; C495680:SLC2A2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein