Staurosporine stimulates insulin gene expression via CRE dependent manner.

We examined various compounds to stimulate the transcription of promoter-reporter construct in pancreatic HIT-T15 cells, that had been stably transfected with the rat insulin I promoter-PLAP reporter gene, and found staurosporine at dose of nanomole enhanced insulin promoter activity significantly. Northern blotting analysis and ELISA (enzyme linked immunosorbent assay) showed that the promoter activity of insulin gene was well correlated with the endogenous level of insulin mRNA and protein in HIT-T15, indicating that staurosporine stimulated the biosynthesis of insulin at levels of transcription and translation. The deletion and point mutation of cAMP response element (CRE) in the promoter region of insulin gene lost the promoter activity of reporter gene induced by staurosporine. These results suggested that insulin promoter activity stimulated by staurosporine is CRE-dependent.