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volume 294 issue 8 pages 2839-5691

Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism

Publication typeJournal Article
Publication date2019-02-01
scimago Q1
wos Q2
SJR1.705
CiteScore7.6
Impact factor3.9
ISSN00219258, 1083351X
Biochemistry
Molecular Biology
Cell Biology
Abstract
The mechanisms by which metformin (dimethylbiguanide) inhibits hepatic gluconeogenesis at concentrations relevant for type 2 diabetes therapy remain debated. Two proposed mechanisms are 1) inhibition of mitochondrial Complex 1 with consequent compromised ATP and AMP homeostasis or 2) inhibition of mitochondrial glycerophosphate dehydrogenase (mGPDH) and thereby attenuated transfer of reducing equivalents from the cytoplasm to mitochondria, resulting in a raised lactate/pyruvate ratio and redox-dependent inhibition of gluconeogenesis from reduced but not oxidized substrates. Here, we show that metformin has a biphasic effect on the mitochondrial NADH/NAD redox state in mouse hepatocytes. A low cell dose of metformin (therapeutic equivalent:
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GOST |
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GOST Copy
Alshawi A., Agius L. Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism // Journal of Biological Chemistry. 2019. Vol. 294. No. 8. pp. 2839-5691.
GOST all authors (up to 50) Copy
Alshawi A., Agius L. Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism // Journal of Biological Chemistry. 2019. Vol. 294. No. 8. pp. 2839-5691.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1074/jbc.ra118.006670
UR - https://doi.org/10.1074/jbc.ra118.006670
TI - Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism
T2 - Journal of Biological Chemistry
AU - Alshawi, Ahmed
AU - Agius, Loranne
PY - 2019
DA - 2019/02/01
PB - American Society for Biochemistry and Molecular Biology
SP - 2839-5691
IS - 8
VL - 294
PMID - 30591586
SN - 0021-9258
SN - 1083-351X
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2019_Alshawi,
author = {Ahmed Alshawi and Loranne Agius},
title = {Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism},
journal = {Journal of Biological Chemistry},
year = {2019},
volume = {294},
publisher = {American Society for Biochemistry and Molecular Biology},
month = {feb},
url = {https://doi.org/10.1074/jbc.ra118.006670},
number = {8},
pages = {2839--5691},
doi = {10.1074/jbc.ra118.006670}
}
MLA
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MLA Copy
Alshawi, Ahmed, and Loranne Agius. “Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism.” Journal of Biological Chemistry, vol. 294, no. 8, Feb. 2019, pp. 2839-5691. https://doi.org/10.1074/jbc.ra118.006670.