Glucose metabolism in mouse embryos exposed to metformin in vitro.

Metformin is an oral hypoglycaemic agent used to treat patients with non-insulin-dependent diabetes mellitus, but its effect on embryonic tissues has not been well studied. Early-somite mouse embryos were exposed in whole embryo culture to metformin (0-2000mug/ml) and assayed for glucose uptake and glycolysis at 6, 12 and 24 hours. Embryos exposed to metformin for 6 hours were also evaluated for glucose uptake in the presence of 0 or 100 mum cytochalasin B. Glucose uptake was increased in embryos exposed to metformin at 2000mug/ml for 6 hours and 1000mug/ml or more for 12 hours. Glycolysis was increased in embryos exposed to metformin at 2000mug/ml for 6 or 24 hours and 1000mug/ml or more for 12 hours, producing lactate concentrations up to six times higher than controls. Glut-1 was increased in embryos exposed to 1000mug/ml or more for 6 hours, and metformin-stimulated glucose uptake was significantly decreased by cytochalasin B. Thus, glucose uptake and glycolytic metabolism are increased in early-somite mouse embryos in response to high concentrations of metformin in vitro, and the mechanism of increased glucose uptake appears to involve a cytochalasin B-sensitive glucose transporter.