Polonsky K S, Given B D, Van Cauter E
University of Chicago, Pritzker School of Medicine, Illinois 60637.
J Clin Invest. 1988 Feb;81(2):442-8. doi: 10.1172/JCI113339.
The pattern of endogenous insulin secretion over a 24-h period, which included three mixed meals, was evaluated in 14 normal volunteers and 15 obese subjects. Insulin secretory rates were calculated from plasma C-peptide levels using individually derived C-peptide kinetic parameters and a validated open two-compartment model of peripheral C-peptide kinetics. Insulin secretion rates were consistently elevated in the obese subjects under basal conditions (11.6 +/- 1.2 vs. 5.4 +/- 0.5 nmol/h) and in the 4 h after breakfast (139 +/- 15 vs. 63 +/- 5 nmol/4 h, P less than 0.001), lunch (152 +/- 16 vs. 67 +/- 5 nmol/4 h, P less than 0.001), and dinner (145 +/- 18 vs. 65 +/- 6 nmol/4 h, P less than 0.001). In the normal subjects, basal insulin secretion represented 50 +/- 2.1% of total 24-h insulin production, insulin secretion returned to baseline between meals, and equal quantities of insulin were secreted in the 4 h after breakfast, lunch, and dinner, despite the fact that subjects consumed half the number of calories at breakfast compared to lunch and dinner. Overall glucose responses were also similar after the three meals. In contrast, the pattern of insulin secretion in obese subjects was largely normal, albeit set at a higher level. However, the insulin secretion rate after meals did not return to baseline, and the secretion rate immediately before lunch (350.5 +/- 81.9 pmol/min) and dinner (373.6 +/- 64.8 pmol/min) was considerably higher than the secretion rate immediately before breakfast (175.5 +/- 18.5 pmol/min). In these overweight subjects, the glucose response after lunch was lower than after dinner. Analysis of individual 24-h insulin secretory profiles in the normal subjects revealed that insulin secretion was pulsatile. On average 11.1 +/- 0.5 pulses were produced in each 24-h period. The most prevalent temporal distribution of postmeal secretory pulses was two pulses after breakfast and three pulses after both lunch and dinner. Insulin secretion was also pulsatile during the period without meal stimuli: 3.9 +/- 0.3 pulses occurred during the period of overnight sampling and in the 3-h period before ingestion of the breakfast meal. In the obese subjects, the number and timing of secretory pulses was similar to those of normal volunteers, although the amplitude of the pulses was significantly greater. In both groups of subjects, greater than 80% of insulin pulses were concomitant with a pulse in glucose concentration in the postmeal period. The concomitancy rate was significantly lower in the interval without the meal stimuli, averaging 47% in both groups. Thus in obesity, although hypersecretion of insulin can be documented, the temporal pattern of secretion i s largely unaltered, which suggests that the functioning beta cell mass is enhance, but normal regulatory mechanisms influencing secretion are still operative.
在14名正常志愿者和15名肥胖受试者中评估了包括三餐混合饮食在内的24小时内内源性胰岛素分泌模式。使用个体推导的C肽动力学参数和经过验证的外周C肽动力学开放双室模型，根据血浆C肽水平计算胰岛素分泌率。肥胖受试者在基础状态下（11.6±1.2对5.4±0.5 nmol/h）以及早餐后4小时（139±15对63±5 nmol/4 h，P<0.001）、午餐后（152±16对67±5 nmol/4 h，P<0.001）和晚餐后（145±18对65±6 nmol/4 h，P<0.001）的胰岛素分泌率持续升高。在正常受试者中，基础胰岛素分泌占24小时总胰岛素分泌量的50±2.1%，餐间胰岛素分泌恢复到基线水平，尽管早餐摄入的热量仅为午餐和晚餐的一半，但早餐、午餐和晚餐后4小时分泌的胰岛素量相等。三餐后的总体血糖反应也相似。相比之下，肥胖受试者的胰岛素分泌模式基本正常，尽管处于较高水平。然而，餐后胰岛素分泌率未恢复到基线水平，午餐前（350.5±81.9 pmol/min）和晚餐前（373.6±64.8 pmol/min）的分泌率明显高于早餐前（175.5±18.5 pmol/min）。在这些超重受试者中，午餐后的血糖反应低于晚餐后。对正常受试者个体24小时胰岛素分泌谱的分析显示胰岛素分泌是脉冲式的。每个24小时周期平均产生11.1±0.5个脉冲。餐后分泌脉冲最常见的时间分布是早餐后两个脉冲，午餐和晚餐后三个脉冲。在无进餐刺激期间胰岛素分泌也是脉冲式的：过夜采样期间和早餐摄入前3小时内出现3.9±0.3个脉冲。在肥胖受试者中，分泌脉冲的数量和时间与正常志愿者相似，尽管脉冲幅度明显更大。在两组受试者中，超过80%的胰岛素脉冲与餐后血糖浓度的脉冲同时出现。在无进餐刺激的时间段内，同步率显著降低，两组平均为47%。因此，在肥胖状态下，虽然可以证明胰岛素分泌过多，但分泌的时间模式基本未改变，这表明功能性β细胞量增加，但影响分泌的正常调节机制仍然有效。
