Lillioja S, Mott D M, Zawadzki J K, Young A A, Abbott W G, Bogardus C
J Clin Endocrinol Metab. 1986 May;62(5):922-7. doi: 10.1210/jcem-62-5-922.
In vivo "resistance" to the action of insulin on glucose uptake is commonly found in obesity and is characteristic of noninsulin-dependent diabetes mellitus in obese subjects. To investigate the relationship among glucose uptake, glucose oxidation, and nonoxidative glucose disposal (storage) in subjects with normal glucose tolerance, we studied 25 caucasians and 79 southwestern American Indians, including lean and obese subjects in both groups. The euglycemic clamp technique with simultaneous indirect calorimetry was used to determine rates of glucose uptake and glucose oxidation. These studies were performed at two rates of insulin infusion (40 and 400 mU/m2 X min), with resulting mean plasma insulin concentrations of 113 and 1839 microU/ml, respectively. At the lower insulin infusion rate, there was no glucose storage in subjects with a glucose uptake rate of about 2.2 mg/kg fat free mass X min. In contrast, glucose storage accounted for over 45% of the glucose disposal in subjects with glucose uptake rates over 7.0 mg/kg fat free mass X min studied at similar insulin concentrations. At the high insulin infusion rate, over 70% of the difference in glucose uptake between subjects with a low or high capacity for glucose disposal was due to glucose storage. These studies demonstrated that in normal subjects at both physiological and maximally stimulating plasma insulin concentrations, glucose storage is a major factor in distinguishing between those with low or high rates of insulin-mediated glucose disposal. Since glucose storage may be a specifically activated process, we hypothesize that failure to activate glucose storage is a major defect causing in vivo insulin resistance in subjects with normal glucose tolerance.
在肥胖症患者中，常可发现机体对胰岛素作用于葡萄糖摄取存在“抵抗”，这也是肥胖受试者非胰岛素依赖型糖尿病的特征。为了研究糖耐量正常受试者的葡萄糖摄取、葡萄糖氧化和非氧化葡萄糖处置（储存）之间的关系，我们对25名高加索人和79名美国西南部印第安人进行了研究，两组均包括瘦人和肥胖者。采用同时进行间接测热法的正常血糖钳夹技术来测定葡萄糖摄取率和葡萄糖氧化率。这些研究在两种胰岛素输注速率（40和400 mU/m2×min）下进行，相应的平均血浆胰岛素浓度分别为113和1839 microU/ml。在较低的胰岛素输注速率下，葡萄糖摄取率约为2.2 mg/kg去脂体重×min的受试者没有葡萄糖储存。相比之下，在相似胰岛素浓度下进行研究的葡萄糖摄取率超过7.0 mg/kg去脂体重×min的受试者中，葡萄糖储存占葡萄糖处置的45%以上。在高胰岛素输注速率下，葡萄糖处置能力低或高的受试者之间葡萄糖摄取差异的70%以上是由于葡萄糖储存。这些研究表明，在生理和最大刺激血浆胰岛素浓度下的正常受试者中，葡萄糖储存是区分胰岛素介导的葡萄糖处置率低或高的主要因素。由于葡萄糖储存可能是一个特异性激活的过程，我们推测未能激活葡萄糖储存是导致糖耐量正常受试者体内胰岛素抵抗的主要缺陷。
