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 insulin sensitivity was assessed during a hyperinsulinaemic euglycaemic clamp. The effect of centrally injected neuropeptide Y on post-absorptive glucose metabolism was studied using a constant infusion of [6-3H]glucose.

3. Infusion of neuropeptide Y resulted in a 18% increase in glucose requirement during the clamp, suggesting increased peripheral tissue responsiveness to insulin. Neuropeptide Y injection in 10 h fasted rats increased plasma glucose (area under curve 9.9 ± 0.2 versus 9.1 ± 0.1 mmol h−1 I−1, P < 0.01), insulin (103 ± 23 versus 33 ± 8 pmol/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 initial 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 influences glucose metabolism by altering secretion of islet hormones, hepatic glucose production and the peripheral response to insulin.

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