Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity

• 来源期刊: 中国药理学报（英文版）
• 关键词: epicatechin flavonoids hyperglycemia oxidative stress insulin secretion CaMKII signaling pathway GPR40 KN-93 GW1100
• 年，卷（期）: 2018,（5）
• 页码范围: 893-902
• 页数: 10页
• 语种: 英文
• DOI: 10.1038/aps.2017.174

摘要

Epicatechin (EC) is a monomeric flavan-3-ol. We have previously demonstrated that glucose-intolerant rats fed flavan-3-ols exhibit improved pancreatic islet function corresponding with an increase in circulating EC-derived metabolites. Thus, we speculate that EC may act as a cellular signaling molecule in vivo to modulate insulin secretion. In this study we further examined the effects of different concentrations of EC on H202 or hyperglycemia-induced ROS production, as well as on saturated fatty acid (SFA)-impaired glucose-stimulated insulin secretion (GSIS) in INS-1 cell line in vitro. We showed that EC at a high concentration (30 μmol/L),but not a low concentration (0.3 μmol/L),significantly decreased H202 or hyperglycemia-induced ROS production in INS-1 cells. However, EC (0.3 μmol/L) significantly enhanced SFA-impaired GSIS in INS-1 cells. Addition of KN-93,a CaMKII inhibitor,blocked the effect of EC on insulin secretion and decreased CaMKII phosphorylation. Addition of GW1100,a GPR40 antagonist, significantly attenuated EC-enhanced GSIS, but only marginally affected CaMKII phosphorylation. These results demonstrate that EC at a physiological concentration promotes GSIS in SFA-impaired β-cells via activation of the CaMKII pathway and is consistent with its function as a GPR40 ligand. The findings support a role for EC as a cellular signaling molecule in vivo and further delineate the signaling pathways of EC in β-cells.