Increased hypothalamic neuropeptide Y concentration or hyperphagia in streptozotocin-diabetic rats are not mediated by glucocorticoids.

Hypothalamic neuropeptide Y containing neurones are overactive and may mediate hyperphagia in insulin-deficient diabetic rats, but the factors stimulating them remain uncertain. To determine the possible role of glucocorticoids, we investigated the effects of the glucocorticoid receptor blocker mifepristone (RU486) on food intake and regional hypothalamic neuropeptide Y concentrations in streptozotocin-diabetic rats. RU486 (30 mg/kg) or corn oil vehicle control was given orally for 3 weeks to diabetic rats. Food intake and neuropeptide Y levels in the hypothalamic arcuate and paraventricular nuclei were increased in untreated diabetic rat groups (P < 0.01), and though RU486 did increase plasma corticosterone levels (P < 0.01) it did not have any effect on either feeding or neuropeptide Y levels (P = NS). These negative findings suggest that glucocorticoids may not be responsible for increasing hypothalamic neuropeptide Y or for hyperphagia in insulin-deficient diabetes.