Pueyo M E, Clement K, Vaxillaire M, Passa P, Froguel P, Robert J J, Velho G
INSERUM U-367, Paris, France.
Diabetes Care. 1994 Sep;17(9):1015-21. doi: 10.2337/diacare.17.9.1015.
In eight glucokinase (GCK)-deficient subjects, we have investigated insulin secretion rates (ISRs) in response to intravenous arginine. Impairment in the enzymatic activity of mutant GCK leads to a reduced glycolytic flux in beta-cells. This defect translates in vivo as a right shift in the glucose/SR dose-response curve. Insulin secretion in response to other secretagogues has not been reported.
The arginine test was performed immediately after a 2-h hyperglycemic (10 mM) clamp. ISR was computed by deconvolution of peripheral C-peptide levels. Linear regression analyses were performed to assess correlations between the beta-cell secretory responses to the arginine test, an intravenous glucose tolerance test (IVGTT), and a hyperglycemic clamp (areas under the C-peptide curves), and between these parameters and the glucose tolerance status (area under the glucose curve during an oral glucose tolerance test).
Two minutes after the injection of arginine, the increment in ISR was 30.17 +/- 10.01 pmol insulin.kg-1.min-1 in patients and 36.25 +/- 15.46 pmol insulin.kg-1.min-1 in control subjects (P = 0.38). Throughout the experiment, increments in ISR were comparable in both groups. The amount of insulin secreted in response to arginine (0-5 min) was similar in patients and control subjects: 81 +/- 28 vs. 119 +/- 55 pmol/kg (P = 0.16), respectively. The arginine test C-peptide response was not correlated with the IVGTT or hyperglycemic clamp responses. The arginine test and hyperglycemic clamp responses were not correlated to the glucose tolerance status. The best predictor of the glucose tolerance was the C-peptide response to the IVGTT (r2 = 0.78; P = 0.002).
beta-cell secretory increment in response to arginine was found to be in the normal range in GCK-deficient subjects. The arginine test does not seem to reflect either the beta-cell secretory defect or the glucose tolerance status of these subjects. IVGTT seems to be the best predictor of the latter parameter in this population.
在8名葡萄糖激酶（GCK）缺乏的受试者中，我们研究了静脉注射精氨酸后的胰岛素分泌率（ISR）。突变型GCK的酶活性受损导致β细胞糖酵解通量降低。这种缺陷在体内表现为葡萄糖/胰岛素剂量反应曲线右移。尚未有关于其他促分泌剂刺激下胰岛素分泌的报道。
在2小时高血糖（10 mM）钳夹后立即进行精氨酸试验。通过外周C肽水平的反卷积计算ISR。进行线性回归分析以评估β细胞对精氨酸试验、静脉葡萄糖耐量试验（IVGTT）和高血糖钳夹（C肽曲线下面积）的分泌反应之间的相关性，以及这些参数与葡萄糖耐量状态（口服葡萄糖耐量试验期间葡萄糖曲线下面积）之间的相关性。
注射精氨酸2分钟后，患者的ISR增量为30.17±10.01 pmol胰岛素·kg⁻¹·min⁻¹，对照组为36.25±15.46 pmol胰岛素·kg⁻¹·min⁻¹（P = 0.38）。在整个实验过程中，两组的ISR增量相当。患者和对照组对精氨酸（0 - 5分钟）分泌的胰岛素量相似：分别为81±28和119±55 pmol/kg（P = 0.16）。精氨酸试验的C肽反应与IVGTT或高血糖钳夹反应无关。精氨酸试验和高血糖钳夹反应与葡萄糖耐量状态无关。葡萄糖耐量的最佳预测指标是IVGTT的C肽反应（r² = 0.78；P = 0.002）。
发现GCK缺乏受试者对精氨酸的β细胞分泌增量在正常范围内。精氨酸试验似乎不能反映这些受试者的β细胞分泌缺陷或葡萄糖耐量状态。IVGTT似乎是该人群中后者参数的最佳预测指标。
