Effects of metformin on insulin resistance after injury in the rat.

Hyperglycaemia and insulin resistance occur after injury. The effects of the antidiabetic biguanide metformin in injured rats have been studied in order to elucidate the cause of these effects. Metformin (120 mg/kg S. C.) produced a significant hypoglycaemic effect after a 20% dorsal scald but did not affect the blood glucose concentration in non-injured rats. The hypoglycaemic effect did not result from increased insulin secretion. It was associated with a reduction in liver glycogen and an increase in blood lactate concentrations, suggesting that the drug acted by promoting peripheral glucose utilization. This was confirmed by measuring the clearance rate coefficient of [5-3H]glucose. This rate coefficient was significantly increased by metformin treatment (140 mg/kg S. C.) in scalded rats, although it was not affected in non-injured rats. Intravenous glucose tolerance in scalded rats was not improved, probably because of the increased lactate concentration. Metformin (120-160 mg/kg) also produced a hypoglycaemic effect in rats after a 4 hrs period of bilateral hind-limb ischaemia, suggesting that similar metabolic changes occur after these two types of injury.