Modulatory role of adrenergic nerves on dexamethasone-induced islet cell NPY expression in the rat: Evidence from chemical sympathectomy

We previously demonstrated induction of neuropeptide Y (NPY) in rat islet b eta-cells by the glucocorticoid dexamethasone (DEX). Because noradrenergic nerves appear to regulate NPY expression in the central nervous system (CNS ), we investigated whether DEX-induced islet cell expression of NPY could b e modulated by catecholaminergic nerves. Therefore rats were treated with D EX (2 mg/kg, i.p., for 12 days) and received injections of 6-hydroxydopamin e (6-OHDA; 80 mg/kg, i.v., at day 1 or 10). 6-OHDA treatment eliminated isl et adrenergic nerves. The frequency of NPY-immunoreactive islet cells and t he levels of islet cell NPY messenger RNA (mRNA) were markedly lower in rat s given 6-OHDA at day 1 of the DEX-treatment period. In contrast, the frequ ency of NPY-immunoreactive cells and levels of islet cell NPY mRNA in DEX-t reated rats receiving 6-OHDA at day 10 did not differ from those treated wi th DEX alone. The findings suggest that DEX-induced islet cell expression o f NPY is partially dependent on adrenergic nerves and that the effect of sy mpathectomy is exerted at an early stage of the NPY induction.