Transforming growth factor beta induction of insulin gene expression is mediated by pancreatic and duodenal homeobox gene-1 in rat insulinoma cells.

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