Long‐term in vitro treatment of INS‐1 rat pancreatic β‐cells by unsaturated free fatty acids protects cells against gluco‐ and lipotoxicities via activation of GPR40 receptors
Long‐term in vitro treatment of INS‐1 rat pancreatic β‐cells by unsaturated free fatty acids protects cells against gluco‐ and lipotoxicities via activation of GPR40 receptors
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DOI：
10.1111/j.1440-1681.2012.05691.x
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发表时间：
2012-05
影响因子：
2.9
通讯作者：
Ya Tuo;D. Feng;Dengfeng Wang;Jian Sun-;Shengbin Li;Cheng Chen
中科院分区：
文献类型：
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作者：
Ya Tuo;D. Feng;Dengfeng Wang;Jian Sun-;Shengbin Li;Cheng Chen
G蛋白偶联受体40(GPR40)是一种膜结合的G蛋白偶联受体，与中长链游离脂肪酸(FFA)有很高的亲和力。GPR40在胰腺β细胞上的急性激活可引起胰岛素分泌，而长时间激活可能导致饱和脂肪酸对β细胞作用的恶化。已有文献证明，不同类型的游离脂肪酸对胰岛素分泌产生不同的影响；然而，关于β细胞长期暴露于不饱和脂肪酸后，GPR40的表达及其功能的信息很少。本研究检测了不同类型不饱和脂肪酸作用于INS-1β-细胞48h后GPR40的表达和功能。长期暴露于多不饱和α-亚麻酸可显著增加细胞GPR40mRNA和蛋白的表达，但对油酸和亚油酸均无明显影响。免疫细胞化学显示，经α-亚麻酸处理的细胞中含胰岛素颗粒的数量减少，这与细胞中GPR40的表达增加有关。饱和棕榈酸处理细胞48h可显著抑制基础胰岛素分泌和葡萄糖刺激的胰岛素分泌，但不饱和α-亚麻酸处理细胞48h不能抑制基础胰岛素分泌和葡萄糖刺激的胰岛素分泌。通过测试不同的FFA，发现FFA对INS-1细胞基础和葡萄糖刺激的胰岛素分泌的抑制可以通过增加FFA和GPR40表达的不饱和程度来减弱。本研究的结果表明，不饱和脂肪酸长期体外处理INS-1大鼠胰腺β-细胞可保护细胞免受糖和脂毒性，这与GPR40表达增加是一致的。
G‐Protein coupled receptor 40 (GPR40) is a membrane‐bound G‐protein‐coupled receptor with high binding affinity to medium‐ and long‐chain free fatty acids (FFAs). Acute activation of GPR40 on pancreatic β‐cells causes insulin secretion, whereas prolonged activation may contribute to a deterioration of the effect of saturated FFAs on β‐cells. It has been documented that different types of FFAs produce various effects on insulin secretion; however, little information is available regarding the expression of GPR40 and its function after long‐term exposure of β‐cells to unsaturated FFAs. In the present study, GPR40 expression and function were assessed in INS‐1 β‐cells after 48 h exposure to different types of unsaturated FFAs. The mRNA and protein expression of GPR40 was increased significantly by long‐term exposure of cells to polyunsaturated α‐linolenic acid, but not to either oleic acid or linoleic acid. Immunocytochemistry revealed a reduction in the number of insulin‐containing granules in cells treated with α‐linolenic acid, which was correlated with an increase in cellular expression of GPR40. Basal and glucose‐stimulated insulin secretion were markedly suppressed by 48 h treatment of cells with saturated palmitic acid, but not unsaturated α‐linolenic acid. By testing various FFAs, it was found that FFA‐induced suppression of basal and glucose‐stimulated insulin secretion was attenuated by an increase in the degree of unsaturation of the FFAs and GPR40 expression in response to FFA treatment in INS‐1 cells. The results of the present study indicate that long‐term in vitro treatment of INS‐1 rat pancreatic β‐cells by unsaturated FFAs protects the cells against from gluco‐ and lipotoxicities and that this coincides with an increase in GPR40 expression.