Effects of metformin on glucose metabolism of isolated perfused rat skeletal muscle.

It was investigated whether N,N-dimethylbiguanide hydrochloride (metformin) lowers blood glucose levels by stimulating glucose uptake of skeletal muscle using the isolated perfused rat hindquarter. Osborne-Mendel rats were subjected to a special feeding regimen (food intake only 2 h daily) and were treated orally by metformin (125 mg/kg body weight twice daily) or placebo, respectively. The hypoglycemic effect of metformin could be demonstrated. Thereafter, control rats were perfused in the absence, and metformin-treated rats in the presence of added metformin (0.67 microgram/ml perfusate). Neither the basal nor the insulin-stimulated glucose uptake of skeletal muscle was increased by metformin. Lactate and alanine release, O2 uptake as well as the tissue metabolite levels of glucose, lactate, pyruvate, ATP and creatine-P remained unaffected. On the other hand, metformin caused a significant decline of lactate oxidation as well as an elevated glycogen content of skeletal muscle. It is proposed that the inhibition of lactate oxidation may under certain conditions be instrumental in the development of lactic acidosis associated with biguanide therapy.