Chronic norepinephrine infusion and insulin and glucagon secretion in the dog

The effect of epinephrine on glucose homeostasis has been studied extensively in many species, but there is little data on the effects of another catecholamine, norepinephrine. This study was designed to examine the alterations that occur in insulin and glucagon secretion during a chronic low-dose infusion of norepinephrine in free-roaming dogs. A total of four intravenous glucose tolerance tests and insulin-induced hypoglycemia tests were performed on each of five dogs infused with norepinephrine (1.4 g/min) for 3 mo and on each of eight control dogs. The infusion resulted in a threefold increase in plasma norepinephrine without a significant effect on blood pressure. Fasting serum glucose was elevated significantly in the norepinephrine-infused dogs [102.4 +/- 2.1 vs. 92.8 +/- 1.7 (SE) mg/100 ml]. Fasting plasma glucagon was elevated by the norepinephrine infusion (58.4 +/- 7.6 vs. 31.3 +/- 3.1 pg/ml), whereas fasting serum insulin was inhibited (12.3 +/- 1.3 vs 16.8 +/- 1.7 U/ml). Glucagon secretion in response to hypoglycemia was markedly enhanced in the infused dogs compared with controls. It has been reported that the infusion of norepinephrine in humans will inhibit insulin secretion and increase serum glucose concentrations but have no effect on serum glucagon concentrations. The stimulation of glucagon by norepinephrine has been demonstrated in the isolated, perfused canine pancreas but has not been reported previously in the free-roaming dog.