Transcription factor AP-2β inhibits glucose-induced insulin secretion in cultured insulin-secreting cell-line

Abstract

Aim We previously identified the transcription factor activating enhancer-binding protein-2β (AP-2β) gene as a new candidate for conferring susceptibility to type 2 diabetes. To ascertain the possible involvement of AP-2β in the pathogenesis of type 2 diabetes we examined the effects of AP-2β on glucose-induced insulin secretion. Methods We measured the insulin secretion stimulated by glucose, tolbutamide, or KCl in the HIT-T15 cells infected with adenovirus vectors encoding AP-2β or LacZ (control). Results We identified clear expression of AP-2β in isolated rat pancreatic islets and in HIT-T15 cells. Glucose-induced increase in insulin secretion was significantly inhibited in AP-2β-overexpressing cells (LacZ, 5.0 ± 0.8 ng h −1 mg −1 protein; AP-2β, 1.7 ± 0.2 ng h −1 mg −1 protein; P = 0.0015), whereas insulin expression was the same in both types of cells. Tolbutamide-induced insulin secretion was also suppressed in the AP-2β-overexpressing cells, but KCl-induced insulin secretion was not affected by AP-2β overexpression. In addition, Kir6.2 and glucokinase expression was significantly decreased in the AP-2β-overexpressing cells. Conclusion We identified for the first time that AP-2β expressed and functioned in insulin-secreting cell-line HIT-T15. These results suggest that AP-2β contributes to susceptibility to type 2 diabetes by inhibiting glucose-induced insulin secretion in pancreatic β cells.