Cyanidin Stimulates Insulin Secretion and Pancreatic β-Cell Gene Expression through Activation of L-type Voltage-Dependent Ca2+ Channels

Cyanidin is a natural anthocyanidin present in fruits and vegetables with anti-diabetic properties including stimulation of insulin secretion. However, its mechanism of action remains unknown. In this study, we elucidated the mechanisms of cyanidin for stimulatory insulin secretion from pancreatic beta-cells. Rat pancreatic beta-cells INS-1 were used to investigate the effects of cyanidin on insulin secretion, intracellular Ca2+ signaling, and gene expression. We detected the presence of cyanidin in the intracellular space of beta-cells. Cyanidin stimulated insulin secretion and increased intracellular Ca2+ signals in a concentration-dependent manner. The Ca2+ signals were abolished by nimodipine, an L-type voltage-dependent Ca2+ channel (VDCC) blocker or under extracellular Ca2+ free conditions. Stimulation of cells with cyanidin activated currents typical for VDCCs and up-regulated the expression of glucose transporter 2 (GLUT2), Kir(6.2), and Cav(1.2) genes. Our findings indicate that cyanidin diffuses across the plasma membrane, leading to activation of L-type VDCCs. The increase in intracellular Ca2+ stimulated insulin secretion and the expression of genes involved in this process. These findings suggest that cyanidin could be used as a promising agent to stimulate insulin secretion.