Shapiro E T, Tillil H, Polonsky K S, Fang V S, Rubenstein A H, Van Cauter E
Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637.
J Clin Endocrinol Metab. 1988 Aug;67(2):307-14. doi: 10.1210/jcem-67-2-307.
Peripheral plasma or serum concentrations of glucose, insulin, C-peptide, glucagon, and cortisol and insulin secretory rates (ISR) were determined at 15-min intervals in eight normal subjects during a constant iv infusion of 4.5 mg glucose/kg.min for a 24-h period. During each sampling interval, the secretory rate of insulin was calculated by deconvolution of the peripheral plasma C-peptide concentration using C-peptide kinetic parameters derived after bolus injections of C-peptide in individual subjects. Periodogram analysis of the individual glucose curves demonstrated a circadian rhythm in all subjects, with a major nocturnal acrophase occurring at an average clock time of 0228 h (range, 0045-0350 h). In five of the eight subjects, a minor acrophase occurred at an average time of 1774 h (range, 1530-2045 h). This diurnal variation in plasma glucose levels was not paralleled by a similar pattern in insulin secretion. Although glucose was infused at a constant rate, significant pulses were found in glucose, insulin, and C-peptide levels and ISR; the pulse durations of these parameters were 182 +/- 30 (+/- SE), 89 +/- 5, 100 +/- 8, and 85 +/- 5 min, respectively, and their periodicities were 208 +/- 33, 106 +/- 7, 114 +/- 10, and 106 +/- 7 min. The durations and frequencies for pulses of insulin, C-peptide, and ISR were not significantly different, whereas glucose pulses had a longer duration and were less frequent (P less than 0.05, by analysis of variance). On the average, 54 +/- 9% of the C-peptide pulses and 47 +/- 8% of the ISR pulses were concomitant with a pulse in glucose levels. Moreover, approximately half of the C-peptide and ISR pulses that were not concomitant with a glucose pulse occurred in synchrony with a shoulder on the up-stroke or down-stroke of glucose pulses. Analysis of glucagon and cortisol profiles revealed no significant associations with the insulin and glucose oscillations. In conclusion, during a constant glucose infusion in normal subjects, regular oscillations of insulin secretion occur at 80- to 120-min intervals. Their tight coupling with glucose oscillations and the lack of association with fluctuations of glucagon and cortisol suggest that these oscillations represent a dynamic property of the insulin-glucose feedback loop.
在8名正常受试者中，以4.5毫克葡萄糖/千克·分钟的恒定速率静脉输注葡萄糖24小时，期间每隔15分钟测定外周血浆或血清中的葡萄糖、胰岛素、C肽、胰高血糖素、皮质醇浓度以及胰岛素分泌率（ISR）。在每个采样间隔期间，利用个体受试者静脉注射C肽后得出的C肽动力学参数，通过对外周血浆C肽浓度进行反卷积计算胰岛素分泌率。对个体葡萄糖曲线进行的周期图分析表明，所有受试者均存在昼夜节律，主要夜间高峰相位平均出现在0228时（范围为0045 - 0350时）。在8名受试者中的5名中，次要高峰相位平均出现在1774时（范围为1530 - 2045时）。血浆葡萄糖水平的这种昼夜变化在胰岛素分泌方面并未呈现出类似模式。尽管葡萄糖以恒定速率输注，但在葡萄糖、胰岛素、C肽水平和ISR中发现了显著的脉冲；这些参数的脉冲持续时间分别为182±30（±标准误）、89±5、100±8和85±5分钟，其周期分别为208±33、106±7、114±10和106±7分钟。胰岛素、C肽和ISR脉冲的持续时间和频率无显著差异，而葡萄糖脉冲持续时间更长且频率更低（方差分析，P<0.05）。平均而言，54±9%的C肽脉冲和47±8%的ISR脉冲与葡萄糖水平的脉冲同时出现。此外，大约一半未与葡萄糖脉冲同时出现的C肽和ISR脉冲与葡萄糖脉冲上升或下降过程中的肩部同步出现。对胰高血糖素和皮质醇谱的分析显示，它们与胰岛素和葡萄糖振荡无显著关联。总之，在正常受试者进行恒定葡萄糖输注期间，胰岛素分泌以80至120分钟的间隔出现有规律的振荡。它们与葡萄糖振荡紧密耦合，且与胰高血糖素和皮质醇波动缺乏关联，这表明这些振荡代表了胰岛素 - 葡萄糖反馈回路的动态特性。
