BEHAVIORAL AND PHYSIOLOGICAL EFFECTS OF 2-DEOXYGLUCOSE INFUSIONS

2-脱氧葡萄糖输注的行为和生理影响

• 批准号: 6160373
• 负责人: D GEORGE
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160373
• 关键词: adrenocorticotropic hormone; alcoholism /alcohol abuse; appetite regulatory center; behavioral /social science research tag; caloric dietary content; clinical research; deoxyglucose; dietary carbohydrates; drug withdrawal; glucose metabolism; human subject; hypothalamus; neuroendocrine system; nutrition related tag; psychophysiology

2-deoxyglucose (2-DG) is a glucose analog which competitively inhibits glucose-6-phosphate dehydrogenase and leads to intracellular glucoprivation. In previous studies, 2-DG has been used as a stressor to activate the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic adrenal axis and the appetitive centers of the hypothalamus. Our interest in this paradigm was generated by the clinical observation that alcoholics frequently consume increased amounts of carbohydrates following cessation of drinking. In order to explore possible hypothalamic abnormalities in patients with alcoholism, we administered 2-DG to abstinent alcoholics and measured the resulting behavioral and physiological changes arising from the 2-DG challenge. We postulated that a 2-DG induced glucoprivic response would give rise to both neuroendocrine and behavioral changes that might elucidate mechanisms of alcohol's action in the hypothalamus. Analysis of the results show alcoholics consume less calories than controls following both 2-DG and placebo administration. Conversely, alcoholics show an exaggerated hypothalamic, ACTH response to glucoprivation. To address the issue of whether this increased response is an acute effect of alcohol withdrawal, the study is now being expanded to include alcoholics who have been alcohol-free for at least six months.

2-脱氧葡萄糖（2-DG）是竞争性抑制 葡萄糖-6-磷酸脱氢酶，并导致细胞内 葡萄糖缺乏 在以前的研究中，2-DG被用作应激源 为了激活下丘脑-垂体-肾上腺（HPA）轴， 交感肾上腺轴和下丘脑的食欲中心。 我们对这一范例的兴趣是由临床观察产生的， 酗酒者经常摄入更多的碳水化合物 停止饮酒后。 为了探索可能的 酗酒患者的下丘脑异常，我们给予 2-DG的戒酒者，并测量由此产生的行为和 生理变化引起的2-DG挑战。 我们假设 2-DG诱导的葡萄糖缺乏反应会引起 神经内分泌和行为变化，可能阐明的机制， 酒精在下丘脑的作用 结果分析表明， 饮酒者摄入的卡路里比对照组少， 安慰剂给药。 相反，酗酒者表现出夸张的 下丘脑，ACTH对葡萄糖缺乏的反应。 为了解决 这种增强的反应是否是酒精戒断的急性效应， 这项研究现在正在扩大到包括酗酒者， 至少六个月不喝酒