Mitochondria to plasma membrane redox signaling is essential for fatty acid β-oxidation-driven insulin secretion.

ABSTRACT: 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 K_ATP-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

SUBMITTER: Jaburek M 

PROVIDER: S-EPMC11332078 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature