Contribution of Mitochondria to Insulin Secretion by Various Secretagogues

0557977 - FGÚ 2023 RIV US eng J - Journal Article
Ježek, Petr - Holendová, Blanka - Jabůrek, Martin - Dlasková, Andrea - Plecitá-Hlavatá, Lydie
Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.
Antioxidants & Redox Signaling. Roč. 36, č. 13 (2022), s. 920-952. ISSN 1523-0864. E-ISSN 1557-7716
R&D Projects: GA ČR(CZ) GA20-00408S
Institutional support: RVO:67985823
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)
Impact factor: 6.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1089/ars.2021.0113

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.
Permanent Link: http://hdl.handle.net/11104/0331854