Central but not peripheral glucocorticoid infusion in adrenalectomized male rats increases basal and substrate-induced insulinemia through a parasympathetic pathway

Objective: Glucocorticoids acting through the central nervous system are po stulated to play a role in the hyperinsulinemia and increased adiposity of obesity. We investigated the role of parasympathetic activation in glucocor ticoid induced hyperinsulinemia. Research Methods and Procedures: Plasma pancreatic polypeptide (PP) levels were used as an index of parasympathetic output. Insulinemia and plasma PP levels were measured basally and after intravenous glucose injection (300 m g/kg) in adrenalectomized male rats infused with dexamethasone (7.5 mug/kg per day) intracerebroventricularly (ICV) or subcutaneously (SC) for 3 to 6 days in the presence or absence of acute atropine blockade (1.0 mg/kg). Foo d intake was controlled between groups. Results: Compared with normal rats, adrenalectomy decreased white adipose t issue depot weights and leptinemia, and these were restored to normal value s by ICV but not SC dexamethasone infusion. Adrenalectomy significantly red uced insulinemia below normal levels, which was restored by SC dexamethason e replacement. However, ICV dexamethasone replacement increased insulinemia of adrenalectomized rats to levels higher than normal control values (basa l, 500 +/- 40 pM vs. 280 +/- 40 pM; 1-minute postglucose, 2500 +/- 180 pM v s. 1240 +/- 260 pM; p < 0.0001) and increased plasma PP levels, which were correlated with insulinemia. Atropine significantly reduced plasma insulin and PP to levels similar to normal controls but had no effect in any other group. Discussion: These data show that glucocorticoids act within the brain to in crease insulinemia, most likely through activation of parasympathetic effer ent fibers. Such an affect would contribute to the adipogenic effects of ce ntral glucocorticoids.