Abstract |
Although transforming growth factor-beta ( TGF-beta) stimulates pancreatic islet cells to synthesize and secret insulin, the mechanism underlying this effect is not known. To investigate this question, we examined the insulin promoter activity focusing on a transcription factor, pancreatic and duodenal homeobox gene-1 (PDX-1) that binds to the A3 element of the rat insulin promoter. Studies performed using the rat insulinoma cell line, INS-1 showed that TGF-beta stimulation of endogenous insulin mRNA expression correlated with increased activity of a reporter construct containing the insulin promoter. A potential mechanism for this increase arose from, electrophoretic mobility shift assay showing that the nuclear extract from TGF-beta treated cells contained higher levels of A3 binding activity. Western blot analysis confirmed that PDX-1 was increased in the nuclear extract from INS-1 cells treated with TGF-beta. As expected, a mutant insulin promoter that lacked the PDX-1 binding site was not stimulated by TGF-beta. In summary, the results of these studies show that TGF-beta stimulates the transcription of insulin gene and this action is mediated by the transcription factor, PDX-1.
|
Authors | Y Sayo, H Hosokawa, H Imachi, K Murao, M Sato, N C Wong, T Ishida, J Takahara |
Journal | European journal of biochemistry
(Eur J Biochem)
Vol. 267
Issue 4
Pg. 971-8
(Feb 2000)
ISSN: 0014-2956 [Print] England |
PMID | 10672004
(Publication Type: Journal Article)
|
Chemical References |
- Homeodomain Proteins
- Insulin
- Nuclear Proteins
- RNA, Messenger
- Receptors, Transforming Growth Factor beta
- Trans-Activators
- Transforming Growth Factor beta
- pancreatic and duodenal homeobox 1 protein
- DNA
- Tacrolimus Binding Proteins
- Immunophilins
- Glucose
- Tacrolimus
|
Topics |
- Animals
- DNA
(genetics, metabolism)
- Glucose
(metabolism, pharmacology)
- Homeodomain Proteins
(metabolism)
- Immunophilins
(genetics)
- Insulin
(genetics)
- Insulinoma
- Islets of Langerhans
(metabolism)
- Mutation
(genetics)
- Nuclear Proteins
(metabolism)
- Promoter Regions, Genetic
(genetics)
- Protein Binding
(drug effects)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Receptors, Transforming Growth Factor beta
(genetics)
- Response Elements
(genetics)
- Tacrolimus
(pharmacology)
- Tacrolimus Binding Proteins
- Trans-Activators
(metabolism)
- Transcriptional Activation
(drug effects)
- Transfection
- Transforming Growth Factor beta
(antagonists & inhibitors, pharmacology)
- Tumor Cells, Cultured
|