Department of Neuroscience, Uppsala University, Box 593, SE-751 24 Uppsala, Sweden.
J Clin Endocrinol Metab. 2012 Feb;97(2):E218-22. doi: 10.1210/jc.2011-2241. Epub 2011 Nov 16.
Animal studies indicate that nicotinamide phosphoribosyltransferase [Nampt/visfatin/pre-B-cell colony-enhancing factor (PBEF)] contributes to the circadian fine-tuning of metabolic turnover. However, it is unknown whether circulating Nampt concentrations, which are elevated in type 2 diabetes and obesity, display a diurnal rhythm in humans.
Our objective was to examine the 24-h profile of serum Nampt in humans under conditions of sleep and sleep deprivation and relate the Nampt pattern to morning postprandial glucose metabolism.
Fourteen healthy men participated in two 24-h sessions starting at 1800 h, including either regular 8-h-night sleep or continuous wakefulness. Serum Nampt and leptin were measured in 1.5- to 3-h intervals. In the morning, plasma glucose and serum insulin responses to standardized breakfast intake were determined.
Under regular sleep-wake conditions, Nampt levels displayed a pronounced diurnal rhythm, peaking during early afternoon (P < 0.001) that was inverse to leptin profiles peaking in the early night. When subjects stayed awake, the Nampt rhythm was preserved but phase advanced by about 2 h (P < 0.05). Two-hour postprandial plasma glucose concentrations were elevated after sleep loss (P < 0.05), whereas serum insulin was not affected. The relative glucose increase due to sleep loss displayed a positive association with the magnitude of the Nampt phase shift (r = 0.54; P < 0.05).
Serum Nampt concentrations follow a diurnal rhythm, peaking in the afternoon. Sleep loss induces a Nampt rhythm phase shift that is positively related to the impairment of postprandial glucose metabolism due to sleep deprivation, suggesting a regulatory impact of Nampt rhythmicity on glucose homeostasis.
动物研究表明,烟酰胺磷酸核糖转移酶[Nampt/内脏脂肪素/前 B 细胞集落增强因子(PBEF)]有助于代谢周转率的昼夜微调。然而,目前尚不清楚循环 Nampt 浓度(在 2 型糖尿病和肥胖症中升高)在人类中是否显示出昼夜节律。
我们的目的是检查睡眠和睡眠剥夺条件下人体血清 Nampt 的 24 小时谱,并将 Nampt 模式与早晨餐后血糖代谢相关联。
14 名健康男性参加了两次 24 小时的会议,从 1800 小时开始,包括正常的 8 小时夜间睡眠或连续清醒。每隔 1.5-3 小时测量血清 Nampt 和瘦素。早晨,确定标准化早餐摄入后血浆葡萄糖和血清胰岛素的反应。
在正常的睡眠-觉醒条件下,Nampt 水平显示出明显的昼夜节律,在下午早些时候达到峰值(P <0.001),与在深夜达到峰值的瘦素曲线相反。当受试者保持清醒时,Nampt 节律得到保留,但相位提前约 2 小时(P <0.05)。睡眠剥夺后两小时餐后血浆葡萄糖浓度升高(P <0.05),而血清胰岛素不受影响。由于睡眠剥夺导致的相对葡萄糖增加与 Nampt 相位偏移的幅度呈正相关(r = 0.54;P <0.05)。
血清 Nampt 浓度呈昼夜节律,下午达到峰值。睡眠剥夺会导致 Nampt 节律相位偏移,与睡眠剥夺导致的餐后血糖代谢受损呈正相关,提示 Nampt 节律性对血糖稳态具有调节作用。