Uncoupling protein 2: A possible link between fatty acid excess and impaired glucose-induced insulin secretion?
Uncoupling protein 2: A possible link between fatty acid excess and impaired glucose-induced insulin secretion?
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DOI：
10.2337/diabetes.50.4.803
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发表时间：
2001-04-01
期刊：
影响因子：
7.7
通讯作者：
Assimacopoulos-Jeannet, F
中科院分区：
文献类型：
--
作者：
Lameloise, N;Muzzin, P;Assimacopoulos-Jeannet, F
已经检查了β细胞长期暴露于升高浓度的脂肪酸改变葡萄糖诱导的胰岛素分泌的机制。将INS-1 β细胞暴露于0.4 mmol/l油酸72 h可增加基础胰岛素分泌，并降低胰岛素释放，以响应高葡萄糖，但不响应作用于K+通道水平（甲苯磺丁脲）或更高水平（KCl升高）的药物。这也抑制了葡萄糖诱导的细胞ATP与ADP比率的增加。油酸暴露后，葡萄糖促进的质膜去极化降低，而KCl的反应是不变的。暴露于游离脂肪酸的细胞表现出较低的线粒体膜电位和减少葡萄糖诱导的超极化。解偶联蛋白（UCP）-2在改变的分泌反应的可能的含义进行了检查，通过测量UCP 2基因表达后，细胞慢性暴露于脂肪酸。油酸盐使UCP 2 mRNA和蛋白质增加2倍。棕榈酸酯和非氧化脂肪酸溴棕榈酸酯对UCP 2 mRNA有类似的影响，表明脂肪酸对UCP 2基因的诱导不需要它们的代谢。这些数据与UCP 2和部分线粒体解偶联在β细胞长期暴露于升高的脂肪酸后观察到的对葡萄糖的分泌反应降低中的作用一致，并表明蛋白质的表达和/或活性可调节响应于葡萄糖的胰岛素分泌。
The mechanism by which long-term exposure of the beta -cell to elevated concentrations of fatty acid alters glucose-induced insulin secretion has been examined. Exposure of INS-1 beta -cells to 0.4 mmol/l oleate for 72 h increased basal insulin secretion and decreased insulin release in response to high glucose, but not in response to agents acting at the level of the K+ channel (tolbutamide) or beyond (elevated KCI). This also suppressed the glucose-induced increase in the cellular ATP-to-ADP ratio. The depolarization of the plasma membrane promoted by glucose was decreased after oleate exposure, whereas the response to KCl was unchanged. Cells exposed to free fatty acids displayed a lower mitochondrial membrane potential and a decreased glucose-induced hyperpolarization. The possible implication of uncoupling protein (UCP)-2 in the altered secretory response was examined by measuring UCP2 gene expression after chronic exposure of the cells to fatty acids. UCP2 mRNA and protein were increased twofold by oleate. Palmitate and the nonoxidizable fatty acid bromopalmitate had similar effects on UCP2 mRNA, suggesting that UCP2 gene induction by fatty acids does not require their metabolism. The data are compatible with a role of UCP2 and partial mitochondrial uncoupling in the decreased secretory response to glucose observed after chronic exposure of the beta -cell to elevated fatty acids, and suggest that the expression and/or activity of the protein may modulate insulin secretion in response to glucose.