Effect of functional adrenalectomy on glucagon secretion and circulating catecholamines during insulin hypoglycemia in the dog

Abstract

The present study was carried out to determine whether an increase in the pancreatic immunoreactive glucagon (IRG) secretion during the acute phase of insulin-induced hypoglycemia depends on circulating catecholamines of adrenal origin. Hypoglycemia was induced by a bolus insulin injection (0.15 IU/kg, i.v.) in dogs anesthetized with sodium pentobarbital (35 mg/kg, i.v.). Plasma aortic epinephrine (E) and norepinephrine (NE) concentrations increased significantly 30 min after the injection of insulin. At this time point, a functional adrenalectomy (diversion of bilateral adrenal venous blood from the systemic circulation) was performed for 5 min. The increased aortic E and NE concentrations significantly decreased reaching, within 5 min, a level below the corresponding preinjection control value. The basal output of pancreatic IRG (6.58 ± 1.12 ng/min, n = 6) significantly increased (24.93 ± 2.77 ng/min, p < 0.05, n = 6) 30 min after insulin injection. During the functional adrenalectomy, the increased pancreatic IRG output diminished rapidly, within 5 min, to approximately 50% (11.73 ± 3.19 ng/min, p < 0.05, n = 6) of the value observed 30 min after insulin administration. In the other group of dogs receiving sham adrenalectomy, the increased aortic E and NE concentrations and pancreatic IRG output following insulin injection remained elevated above the levels observed immediately before the sham adrenalectomy. The net decrease in IRG output during the adrenalectomy was significant (p < 0.05) compared with the corresponding net IRG output observed in the sham group. The net changes in pancreatic IRG output after insulin administration and during adrenalectomy observed in both groups were correlated with those in aortic E and NE concentrations (r = 0.720, p < 0.05). The study shows that the increase in pancreatic IRG secretion during the early phase of insulin-induced hypoglycemia is due, in part, to the increased circulating catecholamines of adrenal origin.Key words: catecholamine, adrenal, pancreas, glucagon, insulin, hypoglycemia, adrenalectomy.