Relative contribution of nervous system and hormones to CNS-mediated hyperglycemia is determined by the neurochemical specificity in the brain.

To determine whether CNS regulatory pathways are organized so that differential sympathetic outflow patterns occur in response to stress, we injected various doses of neostigmine or bombesin into the third cerebral ventricle of fed rats, and then measured the hepatic venous plasma concentrations of glucose, glucagon, insulin, and epinephrine. The following four groups of rats were studied. Group 1 was intact rats. Group 2 comprised intact rats receiving the constant infusion of a) somatostatin to inhibit the endogenous secretion of insulin and glucagon, and b) insulin to maintain the plasma insulin concentration at basal levels. The infusion was started from -30 minutes and given via a catheter in the femoral vein. Group 3 consisted of rats that underwent bilateral adrenal medullectomy (ADMX) one week before the experiment. Group 4 was ADMX rats administered a constant infusion of somatostain with insulin through a femoral vein, as above. The administration of 1 x 10(-9) mol neostigmine caused hepatic venous hyperglycemia mediated by three distinct pathways: 1) direct innervation of the liver, 2) a direct action of epinephrine on the liver, and 3) the action of glucagon on the liver. We estimated the relative contribution of these three factors to be about 47, 32, and 21%, respectively. Relative contributions of three factors of the doses of 5 x 10(-9) and 5 x 10(-8) mol neostigmine demonstrated an effect similar to that of 1 x 10(-9) mol neostigmine. Epinephrine was shown to be the only agent involved in the hyperglycemic response to intraventricular bombesin at doses of 1 x 10(-10), 1 x 10(-9), and 1 x 10(-8) mol.(ABSTRACT TRUNCATED AT 250 WORDS)