Effect of metformin on glucose metabolism in mouse soleus muscle

To investigate the antihyperglycaemic effect of metformin (dimethylbiguanide), insulin binding and glucose metabolism were examined in soleus muscles isolated from streptozotocin diabetic mice. Treatment with metformin (250 mg/kg/day orally for 3 weeks) reduced by 39% the severity of streptozotocin-induced hyperglycaemia. Soleus muscles of metformin treated mice showed a 41% increase in total insulin receptor number, and a 20% increase in 3-0-methylglucose uptake at both submaximally and maximally stimulating insulin concentrations. Oxidation of U-14C-glucose to 14CO2 and the formation of 14C-glycogen were increased by 25% and 30% respectively at maximally stimulating insulin concentrations, but not at submaximally stimulating concentrations. Lactate formation was not significantly altered. Maximum activity of hexokinase (EC 2.7.1.1) was increased by 35%, and this effect was independent of insulin. The results suggest that the antihyperglycaemic effect of metformin in streptozotocin diabetic mice is related in part to an increase in insulin-mediated glucose uptake and oxidative metabolism in skeletal muscle.