Relative contributions of the nervous system and hormones to CNS-mediated hyperglycemia

We quantitatively determined the relative contributions of hormonal factors and the nervous system to the total glucose response after stimulation of the cholinergic neurons in the central nervous system of fed rats. Hepatic venous plasma glucose, glucagon, insulin, epinephrine, and norepinephrine were measured during 120 min after injection of neostigmine (5 X 10(-8) mol) into the third cerebral ventricle in rats subjected to bilateral adrenodemedullation (ADMX) to prevent epinephrine secretion (observed insulin secretion), with and without intravenous infusion of somatostatin to prevent glucagon and insulin secretion. Injection of neostigmine in intact rats resulted in increases in glucose, glucagon, epinephrine, and norepinephrine. Comparison of glucose areas suggests that 22% of the hyperglycemic response is due to the glucagon effect, that 29% is due to the epinephrine effect, and that an unknown factor other than epinephrine or glucagon, which may include activation through direct neural innervation of the liver via alpha-adrenergic receptor, contributes 49%. The suppressive effect of epinephrine on insulin secretion, which is potentially stimulated by direct neural activation of the pancreas, contributes 18% of the net hyperglycemia.