Mitochondrial Superoxide Production Decreases on Glucose-Stimulated Insulin Secretion in Pancreatic beta Cells Due to Decreasing Mitochondrial Matrix NADH/NAD(+) Ratio
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00532352" target="_blank" >RIV/61388971:_____/20:00532352 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/20:00532352
Result on the web
<a href="https://www.liebertpub.com/doi/10.1089/ars.2019.7800" target="_blank" >https://www.liebertpub.com/doi/10.1089/ars.2019.7800</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1089/ars.2019.7800" target="_blank" >10.1089/ars.2019.7800</a>
Alternative languages
Result language
angličtina
Original language name
Mitochondrial Superoxide Production Decreases on Glucose-Stimulated Insulin Secretion in Pancreatic beta Cells Due to Decreasing Mitochondrial Matrix NADH/NAD(+) Ratio
Original language description
Aims:Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells was expected to enhance mitochondrial superoxide formation. Hence, we elucidated relevant redox equilibria. Results:Unexpectedly, INS-1E cells at transitions from 3 (11 mM, pancreatic islets from 5 mM) to 25 mM glucose decreased matrix superoxide release rates (MitoSOX Red monitoring validated by MitoB) and H2O2(mitoHyPer, subtracting mitoSypHer emission). Novel double-channel fluorescence lifetime imaging, approximating free mitochondrial matrix NADH(F,)indicated its similar to 20% decrease. Matrix NAD(F)(+)increased on GSIS, indicated by the FAD-emission lifetime decrease, reflecting higher quenching of FAD by NAD(F)(+). The participation of pyruvate/malate and pyruvate/citrate redox shuttles, elevating cytosolic NADPH(F)(iNAP1 fluorescence monitoring) at the expense of matrix NADH(F), was indicated, using citrate (2-oxoglutarate) carrier inhibitors and cytosolic malic enzyme silencing: All changes vanished on these manipulations.C-13-incorporation from C-13-L-glutamine into C-13-citrate reflected the pyruvate/isocitrate shuttle. Matrix NADPH(F)(iNAP3 monitored) decreased. With decreasing glucose, the suppressor of Complex III site Q electron leak (S3QEL) suppressor caused a higher Complex I I(F)site contribution, but a lower superoxide fraction ascribed to the Complex III site IIIQo. Thus, the diminished matrix NADH(F)/NAD(F)(+) decreased Complex I flavin site I(F)superoxide formation on GSIS. Innovation:Mutually validated methods showed decreasing superoxide release into the mitochondrial matrix in pancreatic beta cells on GSIS, due to the decreasing matrix NADH(F)/NAD(F)(+) (NADPH(F)/NADP(F)(+)) at increasing cytosolic NADPH(F) levels. The developed innovative methods enable real-time NADH/NAD(+)and NADPH/NADP(+) monitoring in any distinct cell compartment. Conclusion:The export of reducing equivalents from mitochondria adjusts lower mitochondrial superoxide production on GSIS, but it does not prevent oxidative stress in pancreatic beta cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10406 - Analytical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Antioxidants & Redox Signaling
ISSN
1523-0864
e-ISSN
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Volume of the periodical
33
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
27
Pages from-to
789-815
UT code for WoS article
000547812000001
EID of the result in the Scopus database
2-s2.0-85091125811