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Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes

ARGAUD, Doriane ; ROTH, Hubert ; WIERNSPERGER, Nicolas ; LEVERVE, Xavier M.

European Journal of Biochemistry, 1993-05, Vol.213 (3), p.1341-1348 [Revista revisada por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes
Autor: ARGAUD, Doriane ; ROTH, Hubert ; WIERNSPERGER, Nicolas ; LEVERVE, Xavier M.
Materias: Adenosine Diphosphate ; Adenosine Diphosphate - analysis ; Adenosine Triphosphate ; Adenosine Triphosphate - analysis ; Animals ; Biochemistry, Molecular Biology ; Biological and medical sciences ; General and cellular metabolism. Vitamins ; Glucagon ; Glucagon - pharmacology ; Gluconeogenesis ; Gluconeogenesis - drug effects ; Lactates ; Lactates - metabolism ; Lactic Acid ; Life Sciences ; Liver ; Liver - drug effects ; Liver - enzymology ; Male ; Medical sciences ; Metformin ; Metformin - pharmacology ; Perfusion ; Pharmacology. Drug treatments ; Pyruvate Kinase ; Pyruvate Kinase - metabolism ; Pyruvates ; Pyruvates - metabolism ; Pyruvic Acid ; Rats ; Rats, Wistar
Es parte de: European Journal of Biochemistry, 1993-05, Vol.213 (3), p.1341-1348
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descripción: Metformin (dimethylbiguanide) has been used for more than 30 years as an antihyperglycemic agent in the treatment of diabetes mellitus, but its effect on gluconeogenesis is still controversial. In isolated hepatocytes from fasted rats, a significant inhibition of glucose production from lactate/pyruvate (10: 1, mol/mol), fructose, alanine or glutamine, following metformin addition, is observed. Moreover, in hepatocytes perifused with dihydroxyacetone as the gluconeogenic substrate and treated with 0.5 mM metformin, an inhibition of the glucose flux and a simultaneous stimulation of the lactate/pyruvate flux were observed. This enhancement of lactate/pyruvate formation appears to be due to an effect on the pyruvate‐kinase enzyme. A direct effect of metformin on pyruvate kinase cannot explain this result, since pyruvate‐kinase activity was not affected by metformin at this concentration. In contrast, the addition of metformin caused a significant decrease in the cellular ATP concentration, a known allosteric inhibitor of this enzyme. This could explain the stimulation of pyruvate‐kinase activity following metformin addition and thus the inhibition of gluconeogenesis.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglés

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Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes

ARGAUD, Doriane ; ROTH, Hubert ; WIERNSPERGER, Nicolas ; LEVERVE, Xavier M.

Oxford, UK: Blackwell Publishing Ltd

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