Role of PDX-1 and MafA as a potential therapeutic target for diabetes.
Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintaining mature beta-cell function. 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 regulates gene expression of various beta-cell-related factors including insulin. Also, PDX-1 has potency to induce insulin-producing cells from non-beta-cells in various tissues, and PDX-1-VP16 fusion protein more efficiently induces insulin-producing cells, especially in the presence of NeuroD or Ngn3. 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, MafA markedly enhances insulin gene promoter activity and ameliorates glucose tolerance in diabetic mice, especially in the presence of PDX-1 and NeuroD. Taken together, PDX-1 and MafA play a crucial role in inducing surrogate beta-cells and could be a therapeutic target for diabetes.
Kaneto
Hideaki
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan. kaneto@medone.med.osaka-u.ac.jp
Miyatsuka
Takeshi
T
Fujitani
Yoshio
Y
Noguchi
Hirofumi
H
Song
Ki-Ho
KH
Yoon
Kun-Ho
KH
Matsuoka
Taka-Aki
TA
D000818:Animals; D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000188:drug therapy*; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology; D007515:Islets of Langerhans / Q000254:growth & development / Q000502:physiology; D051473:Maf Transcription Factors, Large / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein