Cozzolino D, Sessa G, Salvatore T, Sasso F C, Giugliano D, Lefebvre P J, Torella R
Department of Geriatrics and Metabolic Diseases, II University of Naples, Italy.
J Clin Endocrinol Metab. 1996 Feb;81(2):713-8. doi: 10.1210/jcem.81.2.8636293.
The involvement of the opioid system in human obesity has been demonstrated, but whether the abnormalities in the endorphinergic system play a primary role in overfeeding and weight gain or represent a simple biochemical feature is still unclear. The objectives of this study were to investigate the effects of both physiological and pharmacological plasma beta-endorphin levels on some metabolic and hormonal parameters in a normal weight, but prone to obesity, young population consisting of first degree relatives of obese subjects and in body mass index-, sex, and age- matched control subjects without a family history of obesity. Each subject underwent a 1-h infusion of synthetic human beta-endorphin at a constant rate of 4.5 ng/kg.min (low rate), then after a 1-week interval, at a rate of 500 micrograms/h (high rate). Under basal conditions, there was no significant difference in plasma glucose and pancreatic hormones (insulin, C peptide, and glucagon) between the two groups, except for plasma beta-endorphin levels, which were significantly (P < 0.01) higher in relatives of obese individuals. The low rate of beta-endorphin infusion induced physiological elevations of plasma opioid levels in both groups; no significant change in plasma glucose and pancreatic products in control subjects; and a significant (at least P < 0.05) rise in plasma insulin, C peptide, and glucagon concentrations in relatives of the obese. The high rate of beta-endorphin infusion produced pharmacological elevations of opioid plasma levels in both groups; significant (at least P < 0.05) increments in plasma glucose and glucagon levels and no appreciable modification of plasma insulin and C peptide levels in the control group; and a significant (at least P < 0.05) positive response of plasma glucose, insulin, C peptide, and glucagon levels in relatives of obese subjects. These findings suggest that 1) opioid peptides at least in part play a primary, rather than secondary, role in some metabolic events of obesity; and 2) both physiological and pharmacological plasma levels of beta-endorphin are able to provoke marked islet hormone release in the early phase of human obesity.
阿片系统在人类肥胖中的作用已得到证实，但内啡肽能系统的异常在过度进食和体重增加中是起主要作用还是仅代表一种简单的生化特征仍不清楚。本研究的目的是调查生理和药理血浆β-内啡肽水平对正常体重但易肥胖的年轻人群（由肥胖受试者的一级亲属组成）以及体重指数、性别和年龄匹配的无肥胖家族史的对照受试者的一些代谢和激素参数的影响。每位受试者以4.5 ng/kg·min的恒定速率（低速率）接受1小时的合成人β-内啡肽输注，然后在间隔1周后，以500微克/小时的速率（高速率）输注。在基础条件下，两组之间的血浆葡萄糖和胰腺激素（胰岛素、C肽和胰高血糖素）无显著差异，但血浆β-内啡肽水平除外，肥胖个体亲属的血浆β-内啡肽水平显著更高（P < 0.01）。β-内啡肽低速率输注导致两组血浆阿片类物质水平生理性升高；对照受试者的血浆葡萄糖和胰腺产物无显著变化；肥胖亲属的血浆胰岛素、C肽和胰高血糖素浓度显著升高（至少P < 0.05）。β-内啡肽高速率输注使两组的阿片类血浆水平药理学升高；对照组血浆葡萄糖和胰高血糖素水平显著升高（至少P < 0.05），血浆胰岛素和C肽水平无明显变化；肥胖受试者亲属的血浆葡萄糖、胰岛素、C肽和胰高血糖素水平有显著的（至少P < 0.05）阳性反应。这些发现表明：1）阿片肽至少在部分肥胖的某些代谢事件中起主要而非次要作用；2）生理和药理血浆水平的β-内啡肽在人类肥胖早期均能引发显著的胰岛激素释放。
