Effects of metformin on lactate uptake and gluconeogenesis in the perfused rat liver

Dialysis Rounds A Dialysis Case Presentation and Discussion Edited by Roger A. Rodby: Severe Lactic Acidosis Treated with Prolonged Hemodialysis: Recovery After Massive Overdoses of Metformin

“…Metformin can increase lactate production by changing the intracellular redox potential from aerobic to anaerobic metabolism (type B lactic acidosis) (2). Gluconeogenesis is inhibited by metformin through reduced hepatic uptake of lactate (21). Once MALA is established, circulatory failure may worsen the acidosis through reduced tissue perfusion and increased lactate production (a superimposed type A lactic acidosis).…”

Metformin revisited: re‐evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents

“…phosphoenolpyruvate carboxykinase, fructose-1,6bisphosphatase and glucose-6-phosphatase) and activation of pyruvate kinase [38][39][40][41]. Reduction in hepatic uptake of gluconeogenic substrates (lactate and alanine), possibly by depolarization of the hepatocyte membrane, has also been suggested [37,42,43]. Studies have also demonstrated inhibition of mitochondrial respiration by metformin, which may reduce the energy supply required to execute gluconeogenesis [44,45].…”

Metformin and lactic acidosis in diabetic humans

“…This structural difference accounts for differences in pharmacological and metabolic aspects: phenformin is metabolized by aromatic hydroxylation in the liver [19], and is associated with a well-de®ned hyperlactataemic effect by increasing release from skeletal muscle and decreasing oxida-tion [20,21]; in contrast, metformin does not undergo metabolic transformation [14], and does not in¯uence lactate turnover or oxidation in either the basal or the insulin-mediated states [22]. The hyperlactataemic effect of metformin, most noticeably after meals, originates from the splanchnic bed via lactate production by the small intestine [23] and/or defective lactate uptake by the cell liver [24]. At the recommended dosage, this hyperlactataemic effect of metformin is small [25].…”