Interaction between adrenal glucocorticoids and parasympathetic activationin mediating hyperinsulinaemia during long-term central neuropeptide Y infusion in rats

Aims/hypothesis. Hypothalamic neuropeptide Y is implicated in the aetiology of obesity and insulin resistance because of its hyperinsulinaemic, hyperp hagic effects. We investigated the interaction of adrenal glucocorticoids a nd the parasympathetic nervous system in the hyperinsulinaemia caused by ne uropeptide Y infusion in rats. Methods. Neuropeptide Y was intracerebroventricularly given to normal or ad renalectomised rats for 3-6 days with pair-feeding, with or without subcuta neous dexamethasone infusion. We measured basal and intravenous glucose-ind uced insulinaemia and the effect of prior atropine injection. Results. Neuropeptide Y increased basal plasma insulin and C-peptide concen trations (380 +/- 90 and 1000 +/- 60 pmol/l, vs 190 +/- 20 and 590 +/- 50 p mol/l in controls, p < 0.05). Neuropeptide Y also increased the plasma conc entrations of these hormones as early as 60 s after glucose injection (1630 +/- 170 and 3200 +/- 170 pmol/l for insulin and C peptide, respectively, v s 1080 +/- 80 and 1860 +/- 130 pmol/l in controls, p < 0.05). Atropine reve rsed the effect of neuropeptide Y on basal plasma insulin and C-peptide con centrations but had no effect on post-glucose plasma concentrations. The hy perinsulinaemic effects of neuropeptide Y were prevented by adrenalectomy, but were restored by dexamethasone infusion. Dexamethasone in itself did no t statistically significantly increase insulinaemia in adrenalectomised rat s. As in intact rats, atropine attenuated the basal hyperinsulinaemia of ad renalectomised rats that had been infused with neuropeptide Y and dexametha sone but had no effect on post-glucose hyperinsulinaemia. Conclusion/interpretation. These data suggest firstly that neuropeptide Y i nfused centrally induces basal hyperinsulinaemia in rats through glucocorti coid-dependant parasympathetic activation to the pancreas. Secondly, neurop eptide Y potentiates glucose-induced insulinaemia through a pathway dependa nt on adrenal glucocorticoids that cannot be reversed by short-term blockad e of the increased parasympathetic tonus.