THE ROLE OF THE INSULIN CONTROL ELEMENT AND RIPE3B1 ACTIVATORS IN GLUCOSE-STIMULATED TRANSCRIPTION OF THE INSULIN GENE

The most important regulator of insulin expression in islet beta-cells is glucose, which stimulates insulin gene transcription, protein synt hesis, and secretion, Glucose-induced insulin gene transcription is re gulated by cis-acting elements found within the 5'-flanking region of the insulin gene. We previously demonstrated that the insulin control element (ICE, -100 to -91) and RIPE3b1 (-115 to -107) elements mediate d this response in the HIT T-15 beta-cell line. In this study, we exam ined more closely how these insulin gene control elements regulate glu cose-induced transcription. RIPE3b1 element binding was shown to be in duced by glucose in both mouse beta TC-6 and beta TC-3 cell lines, alt hough higher glucose concentrations were necessary in the beta-cells ( beta TC-6) that responded to physiological glucose concentrations. RIP E3b1 binding was also regulated in glucose-stimulated beta-cells by va rious effecters of this response. The RIPE3b1 or ICE elements were sho wn to independently direct glucose-stimulated expression from minimal heterologous promoter constructs, We conclude that the RIPE3b1 and ICE elements are the principal mediators of glucose-stimulated transcript ion of the insulin gene.