Pratley R E, Coon P J, Muller D C, Rogus E M, Goldberg A P
Department of Medicine, University of Maryland at Baltimore.
Exp Gerontol. 1993 Jul-Oct;28(4-5):381-91. doi: 10.1016/0531-5565(93)90065-l.
The hyperinsulinemic euglycemic glucose clamp is widely used to quantitate in vivo insulin action. Modification of this technique by sequentially infusing multiple doses of insulin allows determination of insulin sensitivity and maximal responsiveness; however, the validity of this approach has not been determined in older individuals. In this study, glucose disposal rates during a sequential three-dose clamp at insulin infusion rates of 20, 100, and 500 mU/m2.min were compared to those obtained during a single-dose 100 mU/m2.min clamp in eight healthy older men. There were no differences in plasma insulin levels (256 +/- 46 vs. 261 +/- 32 microU/ml) or glucose disposal rates (11.0 +/- 3.6 vs. 10.8 +/- 3.0 mg/kgfat-free mass.min) during the 100 mU/m2.min infusion of the three-dose clamp and the one-dose clamp. In four subjects with impaired glucose tolerance, the EC50 (insulin concentration producing a half-maximal response) was higher and Mmax (maximal glucose disposal) lower than in subjects with normal glucose tolerance, suggesting impairments in both insulin sensitivity and responsiveness in older subjects with impaired glucose tolerance. Future studies using this modification of the hyperinsulinemic euglycemic glucose clamp to determine insulin sensitivity and responsiveness may lead to an improved understanding of the insulin resistance of aging and the pathogenesis of diseases such as diabetes and hypertension.
高胰岛素正血糖葡萄糖钳夹技术被广泛用于定量体内胰岛素作用。通过依次输注多剂量胰岛素对该技术进行改良，可测定胰岛素敏感性和最大反应性；然而，这种方法在老年人中的有效性尚未得到确定。在本研究中，比较了8名健康老年男性在胰岛素输注速率为20、100和500 mU/m2·min的连续三剂量钳夹期间的葡萄糖处置率与在单剂量100 mU/m2·min钳夹期间获得的葡萄糖处置率。在三剂量钳夹和单剂量钳夹的100 mU/m2·min输注期间，血浆胰岛素水平（256±46对261±32 μU/ml）或葡萄糖处置率（11.0±3.6对10.8±3.0 mg/kg去脂体重·min）没有差异。在4名糖耐量受损的受试者中，半数有效浓度（产生半数最大反应的胰岛素浓度）较高，最大葡萄糖处置量（Mmax）低于糖耐量正常的受试者，这表明糖耐量受损的老年受试者在胰岛素敏感性和反应性方面均受损。未来使用这种改良的高胰岛素正血糖葡萄糖钳夹技术来测定胰岛素敏感性和反应性的研究，可能会增进对衰老胰岛素抵抗以及糖尿病和高血压等疾病发病机制的理解。
