We previously demonstrated induction of neuropeptide Y (NPY) in rat islet beta-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 be modulated by catecholaminergic nerves. Therefore rats were treated with DEX (2 mg/kg, i.p., for 12 days) and received injections of 6-hydroxydopamine (6-OHDA; 80 mg/kg, i.v., at day 1 or 10). 6-OHDA treatment eliminated islet adrenergic nerves. The frequency of NPY-immunoreactive islet cells and the levels of islet cell NPY messenger RNA (mRNA) were markedly lower in rats given 6-OHDA at day 1 of the DEX-treatment period. In contrast, the frequency of NPY-immunoreactive cells and levels of islet cell NPY mRNA in DEX-treated rats receiving 6-OHDA at day 10 did not differ from those treated with DEX alone. The findings suggest that DEX-induced islet cell expression of NPY is partially dependent on adrenergic nerves and that the effect of sympathectomy is exerted at an early stage of the NPY induction.