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Type 2 Diabetes - From Pathophysiology to Cyber Systems
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SYSNO ASEP 0551050 Druh ASEP M - Kapitola v monografii Zařazení RIV C - Kapitola v knize Název Redox Signaling is Essential for Insulin Secretion Tvůrce(i) Ježek, Petr (FGU-C) RID, ORCID
Holendová, Blanka (FGU-C) RID, ORCID, SAI
Jabůrek, Martin (FGU-C) ORCID, RID
Tauber, Jan (FGU-C) RID, ORCID
Dlasková, Andrea (FGU-C) RID, ORCID
Plecitá-Hlavatá, Lydie (FGU-C) RID, ORCIDZdroj.dok. Type 2 Diabetes - From Pathophysiology to Cyber Systems. - London : IntechOpen, 2021 / Stoian Pantea A. - ISBN 978-1-83881-905-7 Rozsah stran s. 33-63 Poč.str. 31 s. Poč.str.knihy 426 Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova pancreatic beta-cells ; insulin secretion ; redox signaling ; NADPH oxidase 4 ; branched chain ketoacid oxidation ; fatty acid beta-oxidation ; ATP-sensitive K+ channel ; GLP1 ; GPR40 Obor OECD Endocrinology and metabolism (including diabetes, hormones) CEP GA20-00408S GA ČR - Grantová agentura ČR Institucionální podpora FGU-C - RVO:67985823 DOI 10.5772/intechopen.94312 Anotace In this review, we place redox signaling in pancreatic beta-cells to the context with signaling pathways leading to insulin secretion, acting for example upon the action of incretins (GLP-1, GIP) and the metabotropic receptor GPR40. Besides a brief description of ion channel participation in depolarization/repolarization of the plasma membrane, we emphasize a prominent role of the elevated glucose level in pancreatic beta-cells during glucose-stimulated insulin secretion (GSIS). We focus on our recent findings, which revealed that for GSIS, not only elevated ATP synthesis is required, but also fundamental redox signaling originating from the NADPH oxidase 4- (NOX4-) mediated H2O2 production. We hypothesized that the closing of the ATP-sensitive K+ channel (KATP) is only possible when both ATP plus H2O2 are elevated in INS-1E cells. KATP alone or with synergic channels provides an element of logical sum, integrating both metabolic plus redox homeostasis. This is also valid for other secretagogues, such as branched chain ketoacids (BCKAs), and partly for fatty acids (FAs). Branched chain aminoacids, leucine, valine and isoleucine, after being converted to BCKAs are metabolized by a series of reactions resembling beta-oxidation of FAs. This increases superoxide formation in mitochondria, including its portion elevated due to the function of electron transfer flavoprotein ubiquinone oxidoreductase (ETF:QOR). After superoxide conversion to H2O2 the oxidation of BCKAs provides the mitochondrial redox signaling extending up to the plasma membrane to induce its depolarization together with the elevated ATP. In contrast, experimental FA-stimulated insulin secretion in the presence of non-stimulating glucose concentrations is predominantly mediated by GPR40, for which intramitochondrial redox signaling activates phospholipase iPLA2γ, cleaving free FAs from mitochondrial membranes, which diffuse to the plasma membrane and largely amplify the GPR40 response. These events are concomitant to the insulin release due to the metabolic component. Hypothetically, redox signaling may proceed by simple H2O2 diffusion or via an SH-relay enabled by peroxiredoxins to target proteins. However, these aspects have yet to be elucidated. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://www.intechopen.com/chapters/73867
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