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

开发使用人血小板体外测量胰岛素敏感性的简单方法。

• 批准号: 09672358
• 负责人: MIZUNO Akira
• 金额: $ 0.38万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672358/
• 关键词: measurement of insulin sensitivity; insulin sensitivity in platelet; platelet aggregation; hyperinsulinemic euglycemic clamp; insulin resistance in diabetics; インスリン抵抗性; 血小板; polycystic ovary syndrom; 糖尿病

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

我们开发了一种利用血液样本血小板作为胰岛素靶器官之一来评估外周组织胰岛素敏感性（IS）的新方法，以简化和缩短门诊糖尿病和/或肥胖患者的胰岛素敏感性（IS）测量。我们定义了 ADP 诱导血小板二次聚集（PSA）的最低浓度（LC），因为我们发现胰岛素对 LC 的作用 ADP诱导的PSA比其他浓度的ADP诱导的PSA大。然后我们在与不同浓度的人重组胰岛素预孵育3分钟后测量ADP诱导的血小板聚集(PA)的LC。在正常受试者中，低胰岛素浓度（0.063或0.125 nmol/l）会引起显着血小板聚集率（PAR）的严重变化；相反，在胰岛素抵抗受试者中，相对较高的胰岛素浓度（大于0.5 nmol/l）会引起PAR的显着变化。因此，我们确定了与没有预孵育胰岛素的基础 PAR 相比，可以引起 PAR 显着变化的最小胰岛素浓度 (MIC)，作为血小板的胰岛素敏感性。并且正常受试者在每个胰岛素浓度下PA的变化均显着大于胰岛素抵抗受试者，我们计算了PAR的总变化（％占PAR总变化的百分比）。然后，我们计算血小板的胰岛素敏感性指数（ISI）。将50名正常受试者、60名糖尿病患者和40名肥胖受试者的ISI值进行对数分布，然后计算log（ISI）值（MISI）作为临床评价值。在临床研究中，我们测量了 10 名正常受试者、12 名糖尿病患者和 10 名肥胖受试者的血小板胰岛素敏感性、高胰岛素正常血糖钳夹和其他代谢标志物。葡萄糖输注率（GIR）与MISI之间的相关系数分别为0.79（p<0.001），GIR与稳态模型评估（HOMA）之间的相关系数为0.54（p<0.01），GIR与体重指数（BMI）之间的相关系数为0.66（p<0.01）。这些数据表明，体外血小板的胰岛素敏感性将反映体内外周组织的胰岛素敏感性。这些数据表明，测量人类血小板胰岛素敏感性的简单方法将是一种有用的装置，可以轻松快速地评估门诊糖尿病和肥胖症患者的胰岛素抵抗。较少的

项目成果

S.Sakamoto, K.Minami, Y.Niwa, M.Ohnaka, Y.Nakaya, A.Mizuno, M.Kuwajima and K.Shima: "Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM." Diabetes

S.Sakamoto、K.Minami、Y.Niwa、M.Ohnaka、Y.Nakaya、A.Mizuno、M.Kuwajima 和 K.Shima：“运动训练和食物限制对大冢长波内皮依赖性松弛的影响”

M.Zhe: "Ovariation hormore-induced beta-cell hypertrophy contributes to the homeostatic contorol of bbeta-cell mass in OLETF femalerat,a model of type2 diabetes." Diabetologia. 41. 799-805 (1998)

M.Zhe：“卵巢激素诱导的 β 细胞肥大有助于 OLETF 雌性大鼠（2 型糖尿病模型）中 β 细胞质量的稳态控制。”

A.Mizuno: "Extrapancreatic action of truncated glucagon-like peptide-1 in Otsuka Long-Evans Tokushima Fatty rats,an animal model for non-insulin-dependent diabetes mellitus" Metabolism. 46(7). 745-749 (1997)

A.Mizuno：“截短的胰高血糖素样肽-1 在大冢朗-埃文斯德岛脂肪大鼠中的胰外作用，这是一种非胰岛素依赖型糖尿病的动物模型”代谢。

A.Mizuno: "Leptin affects pancreatic endocrine functions through the sympathetic nervous system." Erdocrinology. 139(9). 3863-3870 (1998)

A.Mizuno：“瘦素通过交感神经系统影响胰腺内分泌功能。”

K.Ishida: "Leptin suppress basal insulin secretion from rat pancreatic islets" Regulatory Peptides. 70. 179-182 (1997)

K.Ishida：“瘦素抑制大鼠胰岛的基础胰岛素分泌”调节肽。