Effects of Metformin on Glucose Metabolism of Perfused Rat Livers

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2010 Mar 11

PMID 20217188

Citations 7

Authors

Francielli Maria de Souza Silva

Mario Henrique Rocha Alves da Silva

Adelar Bracht

Gabrielle Jacklin Eller

Rodrigo Polimeni Constantin

Nair Seiko Yamamoto

Affiliations

Soon will be listed here.

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.

Citing Articles

Inhibition of Gluconeogenesis by Boldine in the Perfused Liver: Therapeutical Implication for Glycemic Control.

Silva L, de Souza G, Pateis V, Ames-Sibin A, Paes Silva B, Bracht L Int J Hepatol. 2023; 2023:1283716.

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Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model.

Posma R, Venema L, Huijink T, Westerkamp A, Wessels A, De Vries N BMJ Open Diabetes Res Care. 2020; 8(1).

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Quantification of Low-Level Drug Effects Using Real-Time, in vitro Measurement of Oxygen Consumption Rate.

Neal A, Rountree A, Philips C, Kavanagh T, Williams D, Newham P Toxicol Sci. 2015; 148(2):594-602.

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In Vitro Anti-Echinococcal and Metabolic Effects of Metformin Involve Activation of AMP-Activated Protein Kinase in Larval Stages of Echinococcus granulosus.

Loos J, Cumino A PLoS One. 2015; 10(5):e0126009.

PMID: 25965910 PMC: 4429119. DOI: 10.1371/journal.pone.0126009.

Metformin and metabolic diseases: a focus on hepatic aspects.

Zheng J, Woo S, Hu X, Botchlett R, Chen L, Huo Y Front Med. 2015; 9(2):173-86.

PMID: 25676019 PMC: 4567274. DOI: 10.1007/s11684-015-0384-0.

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