Redox Signaling is Essential for Insulin Secretion
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Redox Signaling is Essential for Insulin Secretion
Original language description
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.
Czech name
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Czech description
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Classification
Type
C - Chapter in a specialist book
CEP classification
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OECD FORD branch
30202 - Endocrinology and metabolism (including diabetes, hormones)
Result continuities
Project
<a href="/en/project/GA20-00408S" target="_blank" >GA20-00408S: Pancreatic beta cell redox signaling in insulin secretion mechanism and type 2 diabetes etiology</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Book/collection name
Type 2 Diabetes - From Pathophysiology to Cyber Systems
ISBN
978-1-83881-905-7
Number of pages of the result
31
Pages from-to
33-63
Number of pages of the book
426
Publisher name
IntechOpen
Place of publication
London
UT code for WoS chapter
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