Redox Signaling is Essential for Insulin Secretion

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00551050" target="_blank" >RIV/67985823:_____/21:00551050 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.intechopen.com/chapters/73867" target="_blank" >https://www.intechopen.com/chapters/73867</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.5772/intechopen.94312" target="_blank" >10.5772/intechopen.94312</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Redox Signaling is Essential for Insulin Secretion

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Redox Signaling is Essential for Insulin Secretion

Popis výsledku anglicky

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.

Druh

C - Kapitola v odborné knize

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/GA20-00408S" target="_blank" >GA20-00408S: Redoxní signalizace beta buněk pankreatu při sekreci inzulinu a v rozvoji diabetu 2. typu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název knihy nebo sborníku

Type 2 Diabetes - From Pathophysiology to Cyber Systems

ISBN

978-1-83881-905-7

Počet stran výsledku

31

Strana od-do

33-63

Počet stran knihy

426

Název nakladatele

IntechOpen

Místo vydání

London

Kód UT WoS kapitoly

—