Alterations in the glucose-stimulated insulin secretory dose-response curve and in insulin clearance in nondiabetic insulin-resistant individuals
Alterations in the glucose-stimulated insulin secretory dose-response curve and in insulin clearance in nondiabetic insulin-resistant individuals
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DOI：
10.1210/jc.82.6.1834
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发表时间：
1997-06-01
影响因子：
5.8
通讯作者：
Reaven, GM
中科院分区：
文献类型：
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作者：
Jones, CNO;Pei, D;Reaven, GM
在根据胰岛素敏感性分为两组的葡萄糖耐受妇女中，比较了对葡萄糖分级静脉输注的血浆葡萄糖和胰岛素反应。使用胰岛素抑制试验测量胰岛素介导的葡萄糖处置的抵抗，选择研究的女性代表正常人群中胰岛素抵抗的最高和最低四分位数。通过测量葡萄糖、胰岛素和C肽浓度来评估胰腺β细胞对葡萄糖的敏感性，所述葡萄糖、胰岛素和C肽浓度响应于以1、2、3、4、6和8 mg/kg min的速率持续40 min静脉输注葡萄糖。此外，使用C肽动力学的二室模型和C肽清除率的标准参数，通过外周血浆C肽浓度的去卷积，计算每个采样期内对分级葡萄糖输注的胰岛素分泌率。虽然在整个葡萄糖输注过程中血糖浓度仅略高，但胰岛素抵抗受试者的胰岛素浓度约为两倍。当表示为葡萄糖输注研究期间实现的血浆葡萄糖摩尔增量的函数时，胰岛素抵抗女性的血糖浓度高出90%（684 +/- 55 pmol/L vs. 360 +/- 36 pmol/L）。当葡萄糖浓度从5 mmol/L增加到9 mmol/L时，总积分血浆胰岛素反应（P < 0.001）。然而，总积分胰岛素分泌率仅增加37%（1494 +/- 133 vs. 1093 +/- 125 pmol/mmol/L）。min; P < 0.05）。这种差异表明，胰岛素抵抗受试者的胰岛素清除率较低，并且该值的计算，即胰岛素总分泌与血浆胰岛素曲线下面积的比值，在胰岛素抵抗组中显著较低（1.25 +/- 0.05 vs 1.87 +/- 0.16 L/min）。m（2）; P < 0.005）。这些结果表明，胰岛素抵抗的高胰岛素血症是由继发于葡萄糖刺激的胰岛素反应曲线向左偏移的胰岛素分泌增加以及胰岛素清除率降低引起的。
Plasma glucose and insulin responses to a graded iv infusion of glucose were compared in two groups of glucose-tolerant women divided on the basis of their insulin sensitivity. Resistance to insulin-mediated glucose disposal was measured using the insulin suppression test, and the women studied were chosen to represent the highest and lowest quartiles of insulin resistance seen in the normal population. The sensitivity of the pancreatic beta-cell to glucose was assessed by measuring the glucose, insulin, and C peptide concentrations in response to continuous graded iv infusions of glucose at rates of 1, 2, 3, 4, 6, and 8 mg/kg min for 40 min each. In addition, insulin secretion rates in response to the graded glucose infusion, calculated over each sampling period, were derived from deconvolution of peripheral plasma C peptide concentrations, using a two-compartment model of C peptide kinetics and standard parameters for C peptide clearance. Although plasma glucose concentrations were only slightly higher throughout the glucose infusion, the insulin concentrations were approximately doubled in the insulin-resistant subjects. When expressed as a function of the molar increments in plasma glucose achieved during the glucose infusion studies, the insulin-resistant women had a 90% higher (684 +/- 55 vs. 360 +/- 36 pmol/L . mmol/L; P < 0.001) total integrated plasma insulin response as the glucose concentration was increased from 5 to 9 mmol/L. However, the total integrated insulin secretory rate was only increased by 37% (1494 +/- 133 vs. 1093 +/- 125 pmol/mmol/L . min; P < 0.05) in the insulin-resistant group. This discrepancy suggested that insulin clearance was lower in the insulin-resistant subjects, and the calculation of this value, as the ratio of the total secretion of insulin to the area under the plasma insulin curve, was significantly lower in the insulin-resistant group (1.25 +/- 0.05 vs. 1.87 +/- 0.16 L/min . m(2); P < 0.005). These results show that the hyperinsulinemia of insulin resistance results from an increase in insulin secretion secondary to a shift to the left of the glucose-stimulated insulin response curve as well as a decrease in insulin clearance.