我们询问线粒体的急性氧化还原信号是否与胰腺β细胞在低葡萄糖时的脂肪酸(FA)刺激的胰岛素分泌(FASIS)同时存在。我们显示FAβ氧化产生超氧化物/H2O2,提供:i)线粒体到质膜的氧化还原信号,关闭KATP通道与升高的ATP协同作用(在葡萄糖刺激的胰岛素分泌时替代NADPH-氧化酶-4介导的H2O2信号传导);ii)氧化还原敏感性磷脂酶iPLA2γ/PNPLA8的激活,切割线粒体FAs,使代谢型GPR40受体增强胰岛素分泌(IS)。在空腹血糖,wt小鼠的棕榈酸刺激IS;棕榈酸,硬脂酸,月桂,油酸,亚油酸,和己酸也在融合胰岛(PI)中,在iPLA2γ/PNPLA8敲除小鼠/PIs中具有抑制的第一阶段。细胞外/胞质H2O2监测显示不依赖敲除的氧化还原信号,被线粒体抗氧化剂SkQ1,依托莫昔尔,CPT1消音,过氧化氢酶过表达,所有抑制FASIS,保持ATP敏感的K+通道开放,和胞质[Ca2+]振荡减少。小鼠中的FASIS是餐后延迟的生理事件。因此记录了FAβ氧化的氧化还原信号,到达质膜,本质上是共同刺激的。
We asked whether acute redox signaling from mitochondria exists concomitantly to fatty acid- (FA-) stimulated insulin secretion (FASIS) at low glucose by pancreatic β-cells. We show that FA β-oxidation produces superoxide/H2O2, providing: i) mitochondria-to-plasma-membrane redox signaling, closing KATP-channels synergically with elevated ATP (substituting NADPH-oxidase-4-mediated H2O2-signaling upon glucose-stimulated insulin secretion); ii) activation of redox-sensitive phospholipase iPLA2γ/PNPLA8, cleaving mitochondrial FAs, enabling metabotropic GPR40 receptors to amplify insulin secretion (IS). At fasting glucose, palmitic acid stimulated IS in wt mice; palmitic, stearic, lauric, oleic, linoleic, and hexanoic acids also in perifused pancreatic islets (PIs), with suppressed 1st phases in iPLA2γ/PNPLA8-knockout mice/PIs. Extracellular/cytosolic H2O2-monitoring indicated knockout-independent redox signals, blocked by mitochondrial antioxidant SkQ1, etomoxir, CPT1 silencing, and catalase overexpression, all inhibiting FASIS, keeping ATP-sensitive K+-channels open, and diminishing cytosolic [Ca2+]-oscillations. FASIS in mice was a postprandially delayed physiological event. Redox signals of FA β-oxidation are thus documented, reaching the plasma membrane, essentially co-stimulating IS.