EFFECT OF SUSTAINED PHYSIOLOGICAL HYPERINSULINEMIA ON HYPOTHALAMIC NEUROPEPTIDE-Y AND NPY MESSENGER-RNA LEVELS IN THE RAT

Neuropeptide Y (NPY) synthesized in the arcuato-paraventricular projec tion in the rat hypothalamus is thought to play an important role in c ontrolling energy homeostasis. The factors that regulate hypothalamic NPY are not known but, amongst others, insulin has been postulated as an inhibitory modulatory agent, To test this hypothesis, normal male r ats were given either insulin (2 units/day) or saline via subcutaneous osmotic minipumps for 3 days. Euglycaemia was maintained by a concomi tant glucose infusion in insulin-infused rats which had peripheral ins ulin levels 5-8 times higher than saline-infused controls. Hyperinsuli naemic rats ate 42% less than controls, but their total energy intake (food intake plus glucose infusion) was higher than that of controls, and they gained more weight than controls during the experimental peri od. Hyperinsulinaemia had no significant effect on hypothalamic NPY mR NA or NPY levels in the arcuate nucleus. NPY concentrations in the par aventricular nucleus were, however, significantly increased by 73% in hyperinsulinaemic rats, but were closely similar to controls in all ot her areas. insulin may act as a satiety factor in that hyperinsulinaem ic rats ate less, but the fact that these animals had increased total energy intake and gained excessive weight suggests that insulin may no t function as an overall regulator of energy balance. In addition, phy siological hyperinsulinaemia does not apparently inhibit NPY gene expr ession in the arcuate nucleus. Due to the lack of effect of hyperinsul inaemia on NPY synthesis in the arcuate nucleus, the elevated NPY conc entrations in the paraventricular nucleus could result from a reductio n of its release, which would be in keeping with the reduction in food intake,