Intracerebroventricular glucocorticoid infusion in normal rats: Induction of parasympathetic-mediated obesity and insulin resistance

Objective: The aims of the present study were to determine whether increase d body weight resulting from intracerebroventricular (ICV) glucocorticoid ( dexamethasone) infusion in normal rats is associated, as in obesity, with c hanges in glucose metabolism and to investigate whether the parasympathetic nervous system is involved in the glucocorticoid-induced effects. Research Methods and Procedures: Male Sprague-Dawley rats were infused with ICV dexamethasone (2.5 mug/d) or its vehicle for 2 days during which food intake, body weight. and basal insulinemia were measured. Eu-glycemic- hype rinsulinemic clamps associated with the labeled 2-deoxyglucose technique we re then performed to determine the total rate of glucose disappearance and the tissue glucose use indices. Similar experiments were carried out in vag otomized rats. Results: Two days of ICV glucocorticoid infusion in normal rats resulted in increases in food intake, body weight, basal insulinemia, and produced dec reases in the insulin-stimulated total rate of glucose disappearance, as we ll as in glucose use indices of all muscle types studied. None of these alt erations was observed when glucocorticoid infusion was carried out in vagot omized rats. Discussion: These data show that central glucocorticoid infusion favors ana bolic processes, such as feeding behavior, body weight gain, and insulin ou tput, while promoting muscle insulin resistance. These effects seem to be m ediated by an activation of the parasympathetic nervous system, because the y all disappear when tested in vagotomized rats.