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)-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 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 in β-cells.

中文翻译：

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INS-1细胞中葡萄糖刺激的胰岛素分泌的表儿茶素增强作用并不取决于其抗氧化活性。

表儿茶素（EC）是一种单体黄烷-3-醇。先前我们已经证明，喂食了flavan-3-ols的葡萄糖不耐受大鼠表现出改善的胰岛功能，这与循环EC衍生代谢产物的增加相对应。因此，我们推测EC可能在体内起细胞信号分子的作用，以调节胰岛素的分泌。在这项研究中，我们进一步研究了不同浓度的EC对INS-1细胞系中H2O2或高血糖诱导的ROS产生以及饱和脂肪酸（SFA）损害的葡萄糖刺激的胰岛素分泌（GSIS）的影响。 。我们表明，高浓度（30μmol/ L）的EC，而不是低浓度（0.3μmol/ L）的EC，可显着降低H2O2或高血糖诱导的INS-1细胞中ROS的产生。然而，EC（0.3μmol/ L）显着增强了INS-1细胞中SFA受损的GSIS。CaNKII抑制剂KN-93的加入阻断了EC对胰岛素分泌的作用，并降低了CaMKII的磷酸化。GPR40拮抗剂GW1100的加入显着减弱了EC增强的GSIS，但对CaMKII磷酸化的影响很小。这些结果证明EC以生理浓度通过CaMKII途径的活化促进SFA受损的β细胞中的GSIS，并且与其作为GPR40配体的功能一致。这些发现支持了EC作为体内细胞信号分子的作用，并进一步描绘了EC在β细胞中的信号传导途径。这些结果证明EC以生理浓度通过CaMKII途径的活化促进SFA受损的β细胞中的GSIS，并且与其作为GPR40配体的功能一致。这些发现支持了EC在体内作为细胞信号分子的作用，并进一步描绘了EC在β细胞中的信号传导途径。这些结果证明EC以生理浓度通过CaMKII途径的活化促进SFA受损的β细胞中的GSIS，并且与其作为GPR40配体的功能一致。这些发现支持了EC作为体内细胞信号分子的作用，并进一步描绘了EC在β细胞中的信号传导途径。