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Acute nutrient regulation of the mitochondrial glutathione redox state in pancreatic ß-cells.
- Source :
- Biochemical Journal; 6/15/2014, Vol. 460 Issue 3, p411-423, 15p
- Publication Year :
- 2014
-
Abstract
- The glucose stimulation of insulin secretion by pancreatic ß- 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 (E<subscript>GSH</subscript>) and signal through changes in thiol oxidation. However, whether nutrients affect EGSH in ß-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 ß-cells and reacted to low concentrations of exogenous H<subscript>2</subscript>O<subscript>2</subscript> and menadione. Under control conditions, cytosolic/nuclear E<subscript>GSH</subscript> was close to -300 mV and unaffected by glucose (from 0 to 30 mM). In comparison, mitochondrial E<subscript>GSH</subscript> was less negative and rapidly regulated by glucose and other nutrients, ranging from -280mVin the absence of glucose to -299mVin 30 mM glucose. These changes were largely independent from changes in intracellular Ca<superscript>2+</superscript> 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, E<subscript>GSH</subscript> in pancreatic ß- cells under control conditions. [ABSTRACT FROM AUTHOR]
- Subjects :
- GENETIC regulation
GLUTATHIONE
PANCREAS
GLUCOSE
INSULIN
REACTIVE oxygen species
Subjects
Details
- Language :
- English
- ISSN :
- 02646021
- Volume :
- 460
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Biochemical Journal
- Publication Type :
- Academic Journal
- Accession number :
- 98505652
- Full Text :
- https://doi.org/10.1042/BJ20131361