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Contribution of Mitochondria to Insulin Secretion by Various Secretagogues
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SYSNO ASEP 0557977 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Contribution of Mitochondria to Insulin Secretion by Various Secretagogues Author(s) Ježek, Petr (FGU-C) RID, ORCID
Holendová, Blanka (FGU-C) RID, ORCID, SAI
Jabůrek, Martin (FGU-C) ORCID, RID
Dlasková, Andrea (FGU-C) RID, ORCID
Plecitá-Hlavatá, Lydie (FGU-C) RID, ORCIDSource Title Antioxidants & Redox Signaling. - : Mary Ann Liebert - ISSN 1523-0864
Roč. 36, č. 13 (2022), s. 920-952Number of pages 33 s. Language eng - English Country US - United States Keywords pancreatic beta-cell metabolism ; insulin secretion ; redox signaling ; mitochondrial Ca2+ transport ; branched-chain ketoacid oxidation ; fatty acid-stimulated insulin secretion ; ATP-sensitive K+ channel ; TRPM channels ; GLP-1 OECD category Endocrinology and metabolism (including diabetes, hormones) R&D Projects GA20-00408S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000688204200001 EID SCOPUS 85130001667 DOI https://doi.org/10.1089/ars.2021.0113 Annotation Significance: Mitochondria determine glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells by elevating ATP synthesis. As the metabolic and redox hub, mitochondria provide numerous links to the plasma membrane channels, insulin granule vesicles (IGVs), cell redox, NADH, NADPH, and Ca2+ homeostasis, all affecting insulin secretion.Recent Advances: Mitochondrial redox signaling was implicated in several modes of insulin secretion (branched-chain ketoacid [BCKA]-, fatty acid [FA]-stimulated). Mitochondrial Ca2+ influx was found to enhance GSIS, reflecting cytosolic Ca2+ oscillations induced by action potential spikes (intermittent opening of voltage-dependent Ca2+ and K+ channels) or the superimposed Ca2+ release from the endoplasmic reticulum (ER). The ATPase inhibitory factor 1 (IF1) was reported to tune the glucose sensitivity range for GSIS. Mitochondrial protein kinase A was implicated in preventing the IF1-mediated inhibition of the ATP synthase.Critical Issues: It is unknown how the redox signal spreads up to the plasma membrane and what its targets are, what the differences in metabolic, redox, NADH/NADPH, and Ca2+ signaling, and homeostasis are between the first and second GSIS phase, and whether mitochondria can replace ER in the amplification of IGV exocytosis.Future Directions: Metabolomics studies performed to distinguish between the mitochondrial matrix and cytosolic metabolites will elucidate further details. Identifying the targets of cell signaling into mitochondria and of mitochondrial retrograde metabolic and redox signals to the cell will uncover further molecular mechanisms for insulin secretion stimulated by glucose, BCKAs, and FAs, and the amplification of secretion by glucagon-like peptide (GLP-1) and metabotropic receptors. They will identify the distinction between the hub beta-cells and their followers in intact and diabetic states. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2023 Electronic address https://doi.org/10.1089/ars.2021.0113
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