Glucose potentiates β-cell function by inducing expression in rat islets.

Impaired pancreatic β-cell function is the primary defect in type 2 diabetes. Glucose is an important regulator of β-cell growth and function; however, the mechanisms that are involved in the chronic adaptation of β cells to hyperglycemia remain largely unknown. In the present study, global gene expression patterns revealed that tryptophan hydroxylase 1 () was the most profound of genes that are up-regulated in rat islets exposed to high glucose. Calcium and cAMP signals synergistically mediated glucose-stimulated transcription in β cells by activating cAMP-responsive element-binding protein and promoting its binding with a promoter. Similar to results, infusion of high glucose also strongly induced expression and serotonin production in rat islets, along with enhanced islet function. Inhibition or knockdown of markedly decreased glucose-potentiated insulin secretion. In contrast, overexpression of augmented glucose-stimulated insulin secretion in rat islets by up-regulating the expression of genes that are related to islet function. In addition, the long-acting glucagon-like peptide 1 receptor agonist, exendin-4, stimulated expression in a glucose-dependent manner. Knockdown of inhibited exendin-4-potentiated insulin secretion in rat islets. These findings suggest that mediates the compensation of islet function induced by glucose, and that promoting expression in pancreatic β cells will provide a new strategy for the treatment of type 2 diabetes mellitus.-Zhang, Y., Deng, R., Yang, X., Xu, W., Liu, Y., Li, F., Zhang, J., Tang, H., Ji, X., Bi, Y., Wang, X., Zhou, L., Ning, G. Glucose potentiates β-cell function by inducing expression in rat islets.