EFFECTS OF INTRAVENOUS NEUROPEPTIDE-Y ON INSULIN-SECRETION AND INSULIN SENSITIVITY IN SKELETAL-MUSCLE IN NORMAL RATS

Intracerebroventricular administration of neuropeptide Y to normal rat s induces a syndrome characterised by obesity, hyperinsulinaemia. insu lin resistance and over expression of the adipose tissue ob gene. Litt le is known about the effect of circulating neuropeptide Y on glucose metabolism, insulin secretion and leptin. We therefore aimed to evalua te the effect of an intravenous infusion of neuropeptide Yon glucose d isposal, endogenous glucose production, whole body glycolytic flux, an d glucose storage as assessed during euglycaemic hyperinsulinaemic cla mp. In addition, the insulin-stimulated glucose utilisation index in i ndividual tissues was measured by the 2-deoxy-[1-H-3]-glucose techniqu e. The effect of neuropeptide Y on insulin secretion was evaluated by hyperglycaemic clamp. Infusion did not induce any change in endogenous glucose production during basal conditions or at the end of the clamp . Glucose disposal was significantly increased in the rats given neuro peptide Y compared with controls (27.8 +/- 1.3 vs 24.3 +/- 1.6 mg.min( -1).kg(-1); p < 0.05) as was the glycolytic flux (18.9 +/- 1.6 vs 14.4 +/- 0.8 mg.min(-1).kg(-1); p < 0.05), while glucose storage was compa rable in the two groups. In skeletal muscle, the glucose utilisation i ndex was increased significantly in rats given neuropeptide Y. The glu cose utilisation index in subcutaneous and epididimal adipose tissue w as not significantly different between the two groups. Plasma leptin w as significantly increased by hyperinsulinaemia, but was not affected by neuropeptide Y infusion. Both the early and late phase of the insul in response to hyperglycaemia were significantly reduced by neuropepti de Y. In conclusion neuropeptide Y infusion may increase insulin-induc ed glucose disposal in normal rats, accelerating its utilisation throu gh the glycolytic pathway, Neuropeptide Y reduces both phases of the i nsulin response to hyperglycaemia.