EFFECT OF SYSTEMIC GLUCAGON ADMINISTRATION ON ACTH-SECRETION IN ANESTHETIZED RATS

The effect of glucagon on ACTH secretion was studied in anaesthetized rats injected with either saline (0.1 ml i.m.) or glucagon (0.02 mg/kg i.m.). For the first 90 min after glucagon injection, plasma ACTH fel l by 50% from the basal value of 23+/-4 pmol/l (mean+/-S.E.M.) to 11+/ -2 (P=0.011), after which an abrupt return to baseline occurred (120 m in value: 26+/-2 pmol/l). In saline injected rats, the baseline ACTH v alue was not significantly different from either the 90 min value or t he 120 min value (27+/-3 vs 21+/-4 and 24+/-3 pmol/l respectively; P>0 .10). Plasma glucose after glucagon peaked at 11.6+/-1.1 mmol/l by 15 min but subsequently fell rapidly, attaining the baseline by 60 min. I nsulin levels increased sharply after glucagon, from 381+/-78 pmol/l t o 3172+/-668 pmol/l at 15 min, and plateaued at approximately 1000 pmo l/l thereafter. No changes in glucose or insulin were seen in saline i njected rats. The magnitude of suppression of ACTH after glucagon was not affected either by sustained hyperinsulinaemia (similar or equal t o 1400 pmol/l), induced with continuous glucose infusion to maintain p lasma glucose>12 mmol/l, or by pretreatment with the long-acting somat ostatin analogue octreotide (50 mu g/kg s.c.). However, the return to baseline between 100 and 120 min was prevented both by hyperinsulinaem ia induced with sustained hyperglycaemia, and by octreotide. It is pos tulated that glucagon may inhibit ACTH secretion either by a direct ef fect on the hypothalamus or indirectly through insulin, which is known to stimulate endogenous somatostatin release.