The Pancreatic beta-Cell: The Perfect Redox System

0541624 - FGÚ 2022 RIV CH eng J - Journal Article
Ježek, Petr - Holendová, Blanka - Jabůrek, Martin - Tauber, Jan - Dlasková, Andrea - Plecitá-Hlavatá, Lydie
The Pancreatic beta-Cell: The Perfect Redox System.
Antioxidants. Roč. 10, č. 2 (2021), č. článku 197. E-ISSN 2076-3921
R&D Projects: GA ČR(CZ) GA20-00408S
Institutional support: RVO:67985823
Keywords : pancreatic beta-cells * insulin secretion * redox signaling * NADPH oxidase 4 * branched-chain ketoacid oxidation * fatty-acid-stimulated insulin secretion * TRPM channels * ATP-sensitive K+ channel * GLP-1 * GPR40
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 7.675, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2076-3921/10/2/197

Pancreatic beta-cell insulin secretion, which responds to various secretagogues and hormonal regulations, is reviewed here, emphasizing the fundamental redox signaling by NADPH oxidase 4- (NOX4-) mediated H2O2 production for glucose-stimulated insulin secretion (GSIS). There is a logical summation that integrates both metabolic plus redox homeostasis because the ATP-sensitive K+ channel (K-ATP) can only be closed when both ATP and H2O2 are elevated. Otherwise ATP would block K-ATP, while H2O2 would activate any of the redox-sensitive nonspecific calcium channels (NSCCs), such as TRPM2. Notably, a 100%-closed K-ATP ensemble is insufficient to reach the -50 mV threshold plasma membrane depolarization required for the activation of voltage-dependent Ca2+ channels. Open synergic NSCCs or Cl- channels have to act simultaneously to reach this threshold. The resulting intermittent cytosolic Ca2+-increases lead to the pulsatile exocytosis of insulin granule vesicles (IGVs). The incretin (e.g., GLP-1) amplification of GSIS stems from receptor signaling leading to activating the phosphorylation of TRPM channels and effects on other channels to intensify integral Ca2+-influx (fortified by endoplasmic reticulum Ca2+). ATP plus H2O2 are also required for branched-chain ketoacids (BCKAs), and partly for fatty acids (FAs) to secrete insulin, while BCKA or FA beta-oxidation provide redox signaling from mitochondria, which proceeds by H2O2 diffusion or hypothetical SH relay via peroxiredoxin “redox kiss” to target proteins.
Permanent Link: http://hdl.handle.net/11104/0319157