Mitchell T H, Ellis R D, Smith S A, Robb G, Cawthorne M A
Beecham Pharmaceuticals Research Division, Great Burgh, Epsom, Surrey, U.K.
Int J Obes. 1989;13(6):757-66.
BRL 35135 is a novel oral agent which, when dosed chronically to obese rodents with abnormal glucose tolerance, improves both insulin sensitivity and glucose tolerance. To study its effect in man, 10 obese patients on a weight-maintaining diet received BRL 35135 2 mg four times per day for 5 days and then 6 mg four times per day for 5 days. Oral 100 g glucose tolerance tests were performed 1 day prior to and 12 h after the 10-day treatment with BRL 35135. Simultaneously, energy expenditure, glucose oxidation and glucose storage were measured by open-circuit indirect calorimetry. No significant changes in body weight occurred during the 10-day treatment with BRL 35135. Areas under the curves for glucose and insulin were reduced following treatment with BRL 35135 (1518 +/- 152 to 1277 +/- 132 mmol/1/3 h, P less than 0.001 and 13.8 +/- 1.7 to 9.5 +/- 1.3 U/l/3 h, P less than 0.01) (mean +/- s.e.m.). In addition, plasma glucose concentrations, 2h post-oral glucose, were reduced significantly (8.7 +/- 1.0 mmol/l to 6.7 +/- 0.78, P less than 0.01). There was no effect of the treatment on glucose-induced thermogenesis and glucose oxidation did not change but glucose storage increased significantly. The results suggest that BRL 35135 improves glucose tolerance by an increase in insulin sensitivity that is independent of body weight. Glucose storage accounted for the increased glucose disposal.
BRL 35135是一种新型口服制剂，长期给予糖耐量异常的肥胖啮齿动物时，可改善胰岛素敏感性和糖耐量。为研究其对人体的作用，10名维持体重饮食的肥胖患者每天4次服用2mg BRL 35135，共5天，然后每天4次服用6mg，共5天。在BRL 35135治疗10天前及治疗10天后12小时进行口服100g葡萄糖耐量试验。同时，通过开路间接量热法测量能量消耗、葡萄糖氧化和葡萄糖储存。在BRL 35135治疗的10天期间体重无显著变化。BRL 35135治疗后葡萄糖和胰岛素曲线下面积减小（1518±152至1277±132mmol/1/3h，P<0.001；13.8±1.7至9.5±1.3U/l/3h，P<0.01）（均值±标准误）。此外，口服葡萄糖后2小时的血浆葡萄糖浓度显著降低（8.7±1.0mmol/l至6.7±0.78，P<0.01）。该治疗对葡萄糖诱导的产热无影响，葡萄糖氧化未改变，但葡萄糖储存显著增加。结果表明，BRL 35135通过增加胰岛素敏感性改善糖耐量，且与体重无关。葡萄糖储存增加导致葡萄糖处置增加。
