Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity
| Autor: | Kaiyuan Yang, Catherine B. Chan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cell signaling endocrine system Benzylamines Carbohydrate metabolism Ligands Benzoates Catechin Cell Line Receptors G-Protein-Coupled 03 medical and health sciences Ca2+/calmodulin-dependent protein kinase Internal medicine Free fatty acid receptor 1 Insulin-Secreting Cells Insulin Secretion medicine Animals Insulin Pharmacology (medical) Pancreatic islet function Receptor Pharmacology Sulfonamides Dose-Response Relationship Drug Chemistry Fatty Acids General Medicine Hydrogen Peroxide Rats 030104 developmental biology Endocrinology Glucose Pyrimidines Saturated fatty acid Phosphorylation Original Article Calcium-Calmodulin-Dependent Protein Kinase Type 2 Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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