INSULIN REQUIREMENT FOR THE ANTIHYPERGLYCEMIC EFFECT OF METFORMIN

1 Insulin-dependent diabetic BB/S rats with little or no endogenous insulin were used to determine whether insulin is required for the acute antihyperglycaemic effect of metformin (dimethylbiguanide). 2 Metformin (250 mg kg(-1), intrajejunally) did not lower the hyperglycaemia in BB/S rats in the absence of exogenous insulin, but metformin;increased by 69% (P < 0.05) the blood glucose-lowering effect of exogenous insulin. 3 Metformin (250 mg kg(-1), intrajejunally) improved glucose disposal in rats with a normal insulin response to an intravenous glucose challenge. Plasma glucose disappearance was increased from 0.7 +/- 0.1 to 2.5 +/- 0.1% min(-1) (P < 0.05). 3 When the insulin response to glucose was suppressed with somatostatin and diazoxide, metformin improved glucose disposal to a similar extent to that in rats with a normal insulin response. Plasma glucose disappearance was increased from 0.24 +/- 0.02 to 1.0 +/- 0.1% min(-1) (P < 0.01). 5 The results indicate that insulin is required for the acute antihyperglycaemic effect of metformin, but the extent of this effect is not proportional to the prevailing insulin concentration.