Glucose‐lowering effect of BTS 67 582

1 The hypoglycaemic effect of BTS 67 582 (1,1‐dimethyl‐2(2‐morpholinophenyl) guanidine fumarate) was studied in normal rats. 2 BTS 67 582 (100 mg kg −1 , p.o.) acutely lowered basal plasma glucose concentrations: onset within 1 h, maximum decrease of >40% at 2–3 h, and partial return to euglycaemia by 5 h. Plasma insulin concentrations were increased: onset within 30 min, maximum increase 3 fold at 1–2 h; returning to normal by 5 h. 3 BTS 67 582 (100 mg kg −1 ) increased (by 56%) the rate of disappearance of plasma glucose during an intravenous glucose tolerance test, accompanied by a 51% increase in insulin concentrations. 4 During hyperglycaemic clamp studies BTS 67 582 (100 mg kg −1 ) increased glucose utilization 3 fold. This was associated with a 3 fold increase in insulin concentrations, even in the presence of adrenaline at a dosage which inhibits glucose‐induced insulin release. 5 When the insulin‐releasing effect of BTS 67 582 (100 mg kg −1 ) was inhibited by infusion of somatostatin, there was no effect on glycaemia. 6 Insulin‐dependent diabetic BB/S rats, which do not produce endogenous insulin, showed no effect of BTS 67 582 (100 mg kg −1 ) on plasma glucose concentrations in the presence or absence of exogenous insulin. 7 The results demonstrate an acute hypoglycaemic effect of BTS 67 582 which appears to result mainly from its potent insulin‐releasing action.