TRANSCRIPTIONAL CONTROL OF PANCREATIC-ISLET HORMONES GENE-EXPRESSION

Initiation of transcription requires transcription factors that recognize specific DNA sequences present in promoters and enhancers of the respective genes. Cell-specific expression of the pancreatic islet hormone genes is conferred by a cell-specific combination of transcription factors. The DNA binding sites and cDNAs of some of them have been characterized. An islet-specific enhancer-binding protein of the rat glucagon gene recognizes also cis-acting elements of the rat insulin I and rat somatostatin genes. Thus identical or related factors may be involved in the expression of these pancreatic genes, reflecting that the different islet cell types arise from a common progenitor cell. The characterization of islet-specific transcription factors may lead to regulatory genes whose products specify islet cell phenotypes during development. Basal transcriptional activity of islet hormone genes can be enhanced by metabolic, humoral or nerval signals via various second messenger systems. Cyclic AMP acts through distinct response elements. The islet cells are electrically excitable and known secretagogues increase electrical activity and elevate cytosolic calcium concentration. Depolarization-induced activation of voltage-dependent calcium channels stimulates rat glucagon gene transcription suggesting that calcium is an intracellular signal for pancreatic islet hormone gene transcription.