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 increased body weight resulting from intracerebroventricular (ICV) glucocorticoid (dexamethasone) infusion in normal rats is associated, as in obesity, with changes 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 microg/d) or its vehicle for 2 days during which food intake, body weight, and basal insulinemia were measured. Euglycemic-hyperinsulinemic clamps associated with the labeled 2-deoxyglucose technique were then performed to determine the total rate of glucose disappearance and the tissue glucose use indices. Similar experiments were carried out in vagotomized rats.

RESULTS

Two days of ICV glucocorticoid infusion in normal rats resulted in increases in food intake, body weight, basal insulinemia, and produced decreases in the insulin-stimulated total rate of glucose disappearance, as well as in glucose use indices of all muscle types studied. None of these alterations was observed when glucocorticoid infusion was carried out in vagotomized rats.

DISCUSSION

These data show that central glucocorticoid infusion favors anabolic processes, such as feeding behavior, body weight gain, and insulin output, while promoting muscle insulin resistance. These effects seem to be mediated by an activation of the parasympathetic nervous system, because they all disappear when tested in vagotomized rats.