Dryden S, Burns S J, Frankish H M, Williams G
Department of Medicine, University of Liverpool, UK.
Eur J Pharmacol. 1997 Dec 11;340(2-3):221-5. doi: 10.1016/s0014-2999(97)01410-6.
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.
下丘脑含神经肽Y的神经元活性过高，可能介导胰岛素缺乏型糖尿病大鼠的摄食亢进，但刺激这些神经元的因素仍不确定。为了确定糖皮质激素的可能作用，我们研究了糖皮质激素受体阻滞剂米非司酮（RU486）对链脲佐菌素诱导的糖尿病大鼠食物摄入量和下丘脑局部神经肽Y浓度的影响。给糖尿病大鼠口服RU486（30mg/kg）或玉米油载体对照，持续3周。未治疗的糖尿病大鼠组下丘脑弓状核和室旁核的食物摄入量和神经肽Y水平升高（P<0.01），虽然RU486确实增加了血浆皮质酮水平（P<0.01），但对摄食或神经肽Y水平均无影响（P=无显著性差异）。这些阴性结果表明，糖皮质激素可能与胰岛素缺乏型糖尿病时下丘脑神经肽Y增加或摄食亢进无关。
