The role of the insulin control element and RIPE3b1 activators in glucose-stimulated transcription of the insulin gene

Abstract

The most important regulator of insulin expression in islet β-cells is glucose, which stimulates insulin gene transcription, protein synthesis, and secretion. Glucose-induced insulin gene transcription is regulated 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 mediated this response in the HIT T-15 β-cell line. In this study, we examined more closely how these insulin gene control elements regulate glucose-induced transcription. RIPE3b1 element binding was shown to be induced by glucose in both mouse βTC-6 and βTC-3 cell lines, although higher glucose concentrations were necessary in the β-cells (βTC-6) that responded to physiological glucose concentrations. RIPE3b1 binding was also regulated in glucose-stimulated β- cells by various effectors of this response. The RIPE3b1 or ICE elements were shown 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 transcription of the insulin gene.