ACUTE EFFECTS OF CENTRAL NEUROPEPTIDE-Y INJECTION ON GLUCOSE-METABOLISM IN FASTED RATS

1. Neuropeptide Y is a potent appetite stimulant and has been found to modulate glucose metabolism when given chronically. The acute effects of neuropeptide on peripheral glucose handling have not been studied in detail. We have studied the acute effects of central nervous system injection of neuropeptide on glucose metabolism in vivo in the rat. 2 . Rats implanted with chronic cannulae in the third cerebral ventricle were injected with either neuropeptide Y or saline and peripheral ins ulin sensitivity was assessed during a hyperinsulinaemic euglycaemic c lamp. The effect of centrally injected neuropeptide Y on post-absorpti ve glucose metabolism was studied using a constant infusion of [6-H-3] glucose. 3. Infusion of neuropeptide Y resulted in a 18% increase in g lucose requirement during the clamp, suggesting increased peripheral t issue responsiveness to insulin, Neuropeptide Y injection in 10 h fast ed rats increased plasma glucose (area under curve 9.9+/-0.2 versus 9. 1+/-0.1 mmol h(-1) l(-1), P<0.01), insulin (103+/-23 versus 33+/-8 pmo l/l, P<0.01, at 30 min) and glucagon (5.5+/-0.5 versus 3.1+/-0.3 pmol/ l, P<0.05, at 30 min). The increase in plasma glucose was due to an in itial increase in the rate of appearance, which peaked between 20 and 30 min after neuropeptide Y infusion; over the entire 90 min 16% more glucose entered the systemic circulation in the neuropeptide Y-treated rats than in control rats, and the total quantity of glucose removed was also greater. 4. Neuropeptide Y in the central nervous system infl uences glucose metabolism by altering secretion of islet hormones, hep atic glucose production and the peripheral response to insulin.