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

Tanyawan Suantawee,Sirichai Adisakwattana,Walter Hsu,Shaomian Yao,Sara Elazab,Henrique Cheng

doi:10.3390/nu9080814

Abstract

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 β-cells. Rat pancreatic β-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 β-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), Kir6.2, and Cav1.2 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.

Highlights

Glucose is the main physiological stimulus for insulin secretion from pancreatic β-cells
Cyanidin exhibits gene-regulatory activity by up-regulating expression of gene-associated insulin secretion. These findings indicate that cyanidin can be considered as a promising agent for stimulating insulin secretion and regulating gene transcriptions related to insulin secretory response
In pancreatic β-cells, voltage-dependent Ca2+ channel (VDCC) are responsible for extracellular Ca2+ influx

Summary

Introduction

Glucose is the main physiological stimulus for insulin secretion from pancreatic β-cells. When glucose enters cells through glucose transporter 2 (GLUT2), it is phosphorylated to glucose-6 phosphate by glucokinase and metabolized to generate ATP. The generation of ATP induces the closure of ATP-sensitive K+ channels (KATP ), which evokes membrane depolarization and the opening of voltage-dependent Ca2+ channels (VDCCs). This increases intracellular Ca2+ concentration and stimulates insulin secretion [1,2]. In type 2 diabetes mellitus (T2DM), the failure of pancreatic β-cells results from chronic exposure to a high level of circulating glucose, which causes insufficient insulin secretion or loss of insulin action at target tissues [3].

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