Development of simple method for a measurement of insulin sensitivity in vitro using human platelet.

为了简化和缩短门诊糖尿病和/或肥胖症患者外周组织胰岛素敏感性(IS)的测定，我们建立了一种新的评估外周组织胰岛素敏感性(IS)的方法--血小板作为胰岛素的靶器官。我们定义了ADP诱导血小板二次聚集(PSA)的最低浓度(LC)，发现ADP诱导的PSA对LC的作用大于ADP诱导的其他浓度的PSA。正常受试者在较低的胰岛素浓度(0.063或0.125 nmol/L)时可引起显著的血小板聚集率(PAR)改变，而胰岛素抵抗者则可在较高的胰岛素浓度(大于0.5nmol/L)时引起显著的PAR改变。因此，我们确定了…的最低胰岛素浓度与未预孵育的基础PAR相比，更能引起PAR的显著变化，表现为对血小板的胰岛素敏感性。且正常受试者各胰岛素浓度下PA的变化明显大于胰岛素抵抗患者，我们计算了PAR的总变化(占PAR总变化的百分比)。然后计算血小板胰岛素敏感指数(ISI)。对50例正常人、60例糖尿病患者和40例肥胖者的ISI值进行对数分布，计算出临床评价值的对数(ISI)值(MISI)。在临床研究中，我们测定了10例正常人、12例糖尿病患者和10例肥胖者的血小板、高胰岛素正血糖钳夹和其他代谢指标的胰岛素敏感性。葡萄糖输注率与MISI的相关系数为0.001.79(p&lt；0.0 1)，与稳态模型评分的相关系数为0.5 4(p&lt；0.0 1)，与体重指数的相关系数为0.66(p&lt；0.0 1)。这些数据表明，体外血小板的胰岛素敏感性可以反映活体外周组织的胰岛素敏感性。这些数据表明，一种简单的测量人血小板胰岛素敏感性的方法将是一种有用的工具，可以方便、快速地评估门诊糖尿病和肥胖症患者的胰岛素抵抗。较少

We developed a novel method for evaluating insulin sensitivity (IS) in peripheral tissues using blood specimen, platelet, as one of the target organ of insulin, in order to simplify and shorten the measurement of IS in outpatients with diabetes and/or obesity.We defined the lowest concentration (LC) of ADP to induce platelet second aggregation (PSA), as we found out that the insulin actions on LC of ADP-induced PSA was larger than that on other concentration of ADP-induced PSA.Then we measured LC of ADP-induced platelet aggregation (PA), after 3 min preincubation with various concentrations of human recombinant insulin. Serious changes of significant plalatetet aggregation rate (PAR) was evoked from a low insulin concentration (0.063 or 0.125 nmol/l) in normal subjects, on the contrary, a significant changes of PAR could be evoked from a relatively high insulin concentration (more than 0.5 nmol/l) in insulin resistant subjects. So we settled, the minimal insulin concentration (MIC) by … More which significant change of PAR could be induced comparing to the basal PAR without preincubation of insulin, as an insulin sensitivity on platelet. And the changes of PA at every insulin concentration in normal subjects was significantly larger than those in insulin resistant subjects, we calculated the total changes in PAR (% of total changes in PAR). After then, we computed the insulin sensitivity index (ISI) of platelet. ISI values in 50 normal subjects, 60 diabetics and 40 obese subjects were distributed logarithmically, then we calculated log (ISI) value (MISI) for clinical evaluation value. In the clinical study, we measured insulin sensitivity on platelet, hyperinsulinemic euglycemic clamp and other metabolic markers in ten normal subjects, 12 diabetics and 10 obese subjects. Correlation coefficient between glucose infusion rate (GIR) and MISI was 0.79 (p<0.001), that between GIR and homeostatic model assessment (HOMA) was 0.54 (p<0.01) and that between GIR and body mass index (BMI) was 0.66 (p<0.01), respectively. These data would demonstrate that insulin sensitivity on platelet in vitro would reflect an insulin sensitivity on peripheral tissues in vivo.These data suggested that an simple method for the measurement of insulin sensitivity on human platelet would be a useful device to evaluate easily and quickly insulin resistance of outpatients with diabetes and obesity. Less