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Regulation of insulin secretion and production of reactive oxygen species by free fatty acids in pancreatic islets

机译:胰岛中游离脂肪酸调节胰岛素分泌和产生活性氧

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Free fatty acids regulate insulin secretion through metabolic and intracellular signaling mechanisms such as induction of malonyl-CoA/long-chain CoA pathway, production of lipids, GPRs (G protein-coupled receptors) activation and the modulation of calcium currents. Fatty acids (FA) are also important inducers of ROS (reactive oxygen species) production in β-cells. Production of ROS for short periods is associated with an increase in GSIS (glucose-stimulated insulin secretion), but excessive or sustained production of ROS is negatively correlated with the insulin secretory process. Several mechanisms for FA modulation of ROS production by pancreatic β-cells have been proposed, such as the control of mitochondrial complexes and electron transport, induction of uncoupling proteins, NADPH oxidase activation, interaction with the renin-angiotensin system, and modulation of the antioxidant defense system. The major sites of superoxide production within mitochondria derive from complexes I and III. The amphiphilic nature of FA favors their incorporation into mitochondrial membranes, altering the membrane fluidity and facilitating the electron leak. The extra-mitochondrial ROS production induced by FA through the NADPH oxidase complex is also an important source of these species in β-cells.
机译:游离脂肪酸通过代谢和细胞内信号传导机制来调节胰岛素分泌,这些机制包括丙二酰辅酶A /长链辅酶A途径的诱导,脂质的产生,GPR(G蛋白偶联受体)的活化和钙电流的调节。脂肪酸(FA)也是β细胞中ROS(活性氧物质)产生的重要诱导剂。短期内ROS的产生与GSIS(葡萄糖刺激的胰岛素分泌)的增加有关,但是ROS的过量或持续产生与胰岛素分泌过程负相关。已经提出了FA调节胰腺β细胞产生ROS的几种机制,例如控制线粒体复合物和电子转运,诱导解偶联蛋白,NADPH氧化酶活化,与肾素-血管紧张素系统的相互作用以及抗氧化剂的调节。防御系统。线粒体内超氧化物产生的主要部位来自复合物I和III。 FA的两亲性质有利于它们掺入线粒体膜中,改变膜的流动性并促进电子泄漏。 FA通过NADPH氧化酶复合物诱导的线粒体ROS产生也是这些在β细胞中的重要来源。

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