24-HOUR PROFILES AND PULSATILE PATTERNS OF INSULIN-SECRETION IN NORMAL AND OBESE SUBJECTS

24-HOUR PROFILES AND PULSATILE PATTERNS OF INSULIN-SECRETION IN NORMAL AND OBESE SUBJECTS
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DOI:
10.1172/jci113339
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发表时间:
1988-02-01
影响因子:
15.9
通讯作者:
VANCAUTER, E
VANCAUTER, E
中科院分区:
医学1区
文献类型:
--
作者:
POLONSKY, KS;GIVEN, BD;VANCAUTER, E

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内源性胰岛素分泌模式超过24小时的时间,其中包括三个混合餐,在14名正常志愿者和15名肥胖受试者进行了评价。胰岛素分泌率计算血浆C肽水平使用单独衍生的C肽动力学参数和一个有效的开放式二室模型的外周C肽动力学。在基础条件下,肥胖受试者的胰岛素分泌率持续升高(11.6 ± 0.9%)。1.2 vs. 5.4.+-。0.5 nmol/h)和早餐后4小时(139. ±. 15对63 +-。5 nmol/4 h,P <0.001),午餐(152. ±. 16对67 +-。5 nmol/4 h,P <0.001),晚餐(145. ±. 18对65 +-。6 nmol/4h,P <0.001)。在正常受试者中,基础胰岛素分泌为50 ± 0.5mg/kg。2.1%的24小时总胰岛素产生量,两餐之间的胰岛素分泌恢复到基线水平,早餐、午餐和晚餐后4小时内分泌等量的胰岛素,尽管受试者早餐时摄入的卡路里数量是午餐和晚餐的一半。三餐后的总体葡萄糖反应也相似。相比之下,肥胖受试者的胰岛素分泌模式基本上是正常的,尽管水平较高。然而,餐后胰岛素分泌率没有恢复到基线,午餐前的分泌率(350.5 ± 0.001)。81.9 pmol/min)和晚餐(373.6 ±. 64.8 pmol/min)显著高于早餐前的分泌速率(175.5 ± 0.05 μ mol/min)。18.5 pmol/min)。在这些超重的受试者中,午餐后的葡萄糖反应低于晚餐后。对正常人24小时胰岛素分泌曲线的分析表明,胰岛素分泌呈脉动性。平均11.1.+-。0.5在每个24小时周期中产生脉冲。餐后分泌脉冲的最普遍的时间分布是早餐后两个脉冲和午餐和晚餐后三个脉冲。在没有膳食刺激的时期胰岛素分泌也是脉动的:3.9. ±. 0.3脉冲发生在过夜取样期间和摄入早餐前3小时期间。在肥胖对象中,分泌脉冲的数量和时间与正常志愿者相似,尽管脉冲的幅度明显更大。在两组受试者中,> 80%的胰岛素脉冲与餐后血糖浓度脉冲同时出现。伴随率显着较低的时间间隔,没有膳食刺激,平均47%,在两组。因此,在肥胖症中,虽然可以记录胰岛素分泌过多,但分泌的时间模式基本上没有改变,这表明功能性β细胞群增强,但影响分泌的正常调节机制仍然有效。
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 < 0.001), lunch (152 .+-. 16 vs. 67 .+-. 5 nmol/4 h, P < 0.001), and dinner (145 .+-. 18 vs. 65 .+-. 6 nmol/4 h, P < 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 objects, 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, > 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 is largely unaltered, which suggested that the functioning beta cell mass is enhanced, but normal regulatory mechanisms influencing secretion are still operative.