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

作　　者：Kaiyuan YANG Catherine B CHAN 

机构地区：[1]Department of Agricultural, Food and Nutritional Science, University of Alberta Edmonton, Alberta, T6G 2E1 Canada [2]Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2P5, Canada

出　　处：《Acta Pharmacologica Sinica》2018年第5期893-902,共10页中国药理学报（英文版）

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 H2O2 or hyperglycemia-induced ROS production, as well as on saturated fatty acid （SFA）-irnpaired 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 H2O2 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 Jn p-cells.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 H2O2 or hyperglycemia-induced ROS production, as well as on saturated fatty acid （SFA）-irnpaired 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 H2O2 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 Jn p-cells.

关 键 词：EPICATECHIN flavonoids HYPERGLYCEMIA oxidative stress insulin secretion CaMKII signaling pathway GPR40 KN-93 GW1100 

分 类 号：Q578[生物学—生物化学] S436.612.2[农业科学—农业昆虫与害虫防治]