Acute nutrient regulation of the mitochondrial glutathione redox state in pancreatic beta-cells

Details

Serval ID
serval:BIB_130B9154798D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Acute nutrient regulation of the mitochondrial glutathione redox state in pancreatic beta-cells
Journal
Biochem J
Author(s)
Takahashi H. K., Santos L. R., Roma L. P., Duprez J., Broca C., Wojtusciszyn A., Jonas J. C.
ISSN
1470-8728 (Electronic)
ISSN-L
0264-6021
Publication state
Published
Issued date
2014
Volume
460
Number
3
Pages
411-23
Language
english
Notes
Takahashi, Hilton K
Santos, Laila R B
Roma, Leticia P
Duprez, Jessica
Broca, Christophe
Wojtusciszyn, Anne
Jonas, Jean-Christophe
eng
Research Support, Non-U.S. Gov't
England
Biochem J. 2014 Jun 15;460(3):411-23. doi: 10.1042/BJ20131361.
Abstract
The glucose stimulation of insulin secretion by pancreatic beta-cells depends on increased production of metabolic coupling factors, among which changes in NADPH and ROS (reactive oxygen species) may alter the glutathione redox state (EGSH) and signal through changes in thiol oxidation. However, whether nutrients affect EGSH in beta-cell subcellular compartments is unknown. Using redox-sensitive GFP2 fused to glutaredoxin 1 and its mitochondria-targeted form, we studied the acute nutrient regulation of EGSH in the cytosol/nucleus or the mitochondrial matrix of rat islet cells. These probes were mainly expressed in beta-cells and reacted to low concentrations of exogenous H2O2 and menadione. Under control conditions, cytosolic/nuclear EGSH was close to -300 mV and unaffected by glucose (from 0 to 30 mM). In comparison, mitochondrial EGSH was less negative and rapidly regulated by glucose and other nutrients, ranging from -280 mV in the absence of glucose to -299 mV in 30 mM glucose. These changes were largely independent from changes in intracellular Ca(2+) concentration and in mitochondrial pH. They were unaffected by overexpression of SOD2 (superoxide dismutase 2) and mitochondria-targeted catalase, but were inversely correlated with changes in NAD(P)H autofluorescence, suggesting that they indirectly resulted from increased NADPH availability rather than from changes in ROS concentration. Interestingly, the opposite regulation of mitochondrial EGSH and NAD(P)H autofluorescence by glucose was also observed in human islets isolated from two donors. In conclusion, the present study demonstrates that glucose and other nutrients acutely reduce mitochondrial, but not cytosolic/nuclear, EGSH in pancreatic beta-cells under control conditions.
Keywords
Animals, Calcium/metabolism, Catalase/metabolism, Cell Nucleus/metabolism, Cytosol/metabolism, Glucose/*pharmacology, Glutathione/*metabolism, HEK293 Cells, Humans, Hydrogen Peroxide/metabolism, Hydrogen-Ion Concentration, Insulin/metabolism, Insulin Secretion, Insulin-Secreting Cells/drug effects/*metabolism, Mitochondria/*drug effects/physiology, NADP/metabolism, Oxidation-Reduction, Rats, Reactive Oxygen Species/metabolism, Vitamin K 3/metabolism
Pubmed
Create date
14/06/2021 8:59
Last modification date
18/09/2021 5:38
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