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Effects of metformin on glucose metabolism of perfused rat livers

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Abstract

Although metformin has been used to treat type 2 diabetes for several decades, the mechanism of its action on glucose metabolism remains controversial. To further assess the effect of metformin on glucose metabolism this work was undertaken to investigate the acute actions of metformin on glycogenolysis, glycolysis, gluconeogenesis, and ureogenesis in perfused rat livers. Metformin (5 mM) inhibited oxygen consumption and increased glycolysis and glycogenolysis in livers from fed rats. In perfused livers of fasted rats, the drug (concentrations higher than 1.0 mM) inhibited oxygen consumption and glucose production from lactate and pyruvate. Gluconeogenesis and ureogenesis from alanine were also inhibited. The cellular levels of ATP were decreased by metformin whereas the AMP levels of livers from fasted rats were increased. Taken together our results indicate that the energy status of the cell is probably compromised by metformin. The antihyperglycemic effect of metformin seems to be the result of a reduced oxidative phosphorylation without direct inhibition of key enzymatic activities of the gluconeogenic pathway. The AMP-activated protein kinase cascade could also be a probable target for metformin, which switches on catabolic pathways such as glycogenolysis and glycolysis, while switches off ATP consuming processes.

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Authors and Affiliations

  1. Faculdade Integrado de Campo Mourão, Campo Mourão, Brazil

    Francielli Maria de Souza Silva

  2. Department of Biochemistry, Laboratory of Liver Metabolism, University of Maringá, 87020900, Maringá, Brazil

    Mário Henrique Rocha Alves da Silva, Adelar Bracht, Gabrielle Jacklin Eller, Rodrigo Polimeni Constantin & Nair Seiko Yamamoto

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  1. Francielli Maria de Souza Silva
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  2. Mário Henrique Rocha Alves da Silva
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  3. Adelar Bracht
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  4. Gabrielle Jacklin Eller
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  5. Rodrigo Polimeni Constantin
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  6. Nair Seiko Yamamoto
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Correspondence to Nair Seiko Yamamoto.

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de Souza Silva, F.M., Rocha Alves da Silva, M.H., Bracht, A. et al. Effects of metformin on glucose metabolism of perfused rat livers. Mol Cell Biochem 340, 283–289 (2010). https://doi.org/10.1007/s11010-010-0429-2

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  • DOI: https://doi.org/10.1007/s11010-010-0429-2

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