THE EFFECT OF DIAMICRON ON THE SECRETION AND ACTION OF INSULIN

We studied, in healthy subjects (n = 4) and in non-insulin-dependent diabetics (n = 4), the effect of a new sulfonylurea, Diamicron(R), on the secretion and action of insulin, using a mathematical model. This model analyzed, during an intravenous glucose tolerance test, the response of the first and second phase of insulin secretion in relation to the variations in blood glucose (insulin secretion) and the rate of decline in the blood glucose curve in relation to the variations in insulin (insulin response). Each subject was studied twice: once after administration of placebo and once after administration of Diamicron(R) 80 mg 90 min after intravenous injection of 300 mg/kg of D-glucose. In healthy subjects, the glucose load after placebo induced an insulin response of 7.4 +/- 1.0 and 11.3 +/- 1.4-mu-U ml-1 min-1 mg-1 dl-1 for the first and second phases, respectively, and an insulin sensitivity evaluated to be 4.7 +/- 0.3 min mu-U-1 ml-1. Following the administration of Diamicron(R), the insulin response to the same glucose load increased two-fold and five-fold for the first and second phases, respectively, and the insulin sensitivity also increased by a factor of 2. In diabetic subjects the insulin response to the glucose load after placebo was markedly decreased (2.2 +/- 0.5 and 2.5 +/- 0.3-mu-U ml-1 min-1 mg-1 dl-1, respectively) as was the insulin sensitivity (2.5 +/- 0.3 min mu-U-1 ml-1). The administration of Diamicron(R) increased all these parameters by a factor of 2. These findings indicate that in healthy subjects and non-insulin-dependent diabetics, Diamicron(R) is a potent hypoglycemic agent which acts by increasing the first and second phase of insulin secretion and by increasing the sensitivity to insulin.