GLUCOCORTICOIDS AND INSULIN - RECIPROCAL SIGNALS FOR ENERGY-BALANCE

Signals that regulate long-term energy balance have been difficult to identify. Increasingly strong evidence indicates that insulin, acting on the central nervous system in part through its effect on neuropepti de Y (NPY), inhibits food intake. We hypothesized that corticosteroids and insulin might serve as interacting, reciprocal signals for energy balance, acting on energy acquisition, in part through their effects on hypothalamic NPY, as well as on energy stores. Because glucocortico ids also stimulate insulin secretion, their role is normally obscured. Glucocorticoids and insulin were clamped in adrenalectomized rats wit h steroid replacement and streptozotocin-induced diabetes. Glucocortic oids stimulated and insulin inhibited NPY mRNA and food intake. Glucoc orticoids inhibited and insulin increased energy gain as determined by the change in body weight. When adrenalectomized diabetic rats were t reated, corticosterone stimulated and insulin inhibited food intake, a nd, respectively, inhibited and increased overall energy gain. More th an 50% of the variance was explained by regression analysis of the two hormones on food intake and body weight. Thus glucocorticoids and ins ulin are major, antagonistic, long-term regulators of energy balance. The effects of corticosterone and insulin on food intake may be mediat ed, in part, through regulation of hypothalamic NPY synthesis and secr etion.