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[摘要]：Free fatty acids (FFAs) acutely stimulate insulin secretion from pancreatic beta-cells, whereas impair beta-cell function following long term exposure. GPR40, a FFAs receptor, has been demonstrated to be activated by both medium and long chain FFAs and played an important role in insulin release. This study was performed to determine the contribution of GPR40 to short- and/or long-term effects of FFAs on glucose-stimulated insulin secretion (GSIS) and the expression of PDX-1 and GLUT2 in pancreatic beta-cells, as well as the intervenient effects of pioglitazone on lipotoxicity of beta-cells. beta TC6 cell line stably expressing GPR40shRNA were established and the intervention of FFAs and pioglitazone on GSIS and expression of PDX-1 and GLUT2 in beta TC6 cells was investigated. Results showed that 1-h exposure to FFAs significantly enhanced GSIS and increased expression of PDX-1 and GLUT2 in pSilencer-control transfected cells, but not in cells transfected with GPR40shRNA. While 48-h exposure to FFAs significantly impaired GSIS in pSilencer-control transfected cells as well as cells transfected with GPR40shRNA. Furthermore, pioglitazone enhanced insulin secretion in pSilencer-control transfected cells exposed to FFAs for 48 h, but not in cells transfected with GPR40shRNA. These results indicate that GPR40 mediates the short-term effects of FFAs on GSIS, but does not mediate the chronic lipotoxicity on beta-cells. The reverse role of pioglitazone on lipotoxicity of beta-cells may be related to GPR40. (C) 2010 Elsevier Inc. All rights reserved. |
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