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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

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

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.[1]

References

  1. Transforming growth factor beta induction of insulin gene expression is mediated by pancreatic and duodenal homeobox gene-1 in rat insulinoma cells. Sayo, Y., Hosokawa, H., Imachi, H., Murao, K., Sato, M., Wong, N.C., Ishida, T., Takahara, J. Eur. J. Biochem. (2000) [Pubmed]
 
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