Reed M J, Meszaros K, Entes L J, Claypool M D, Pinkett J G, Brignetti D, Luo J, Khandwala A, Reaven G M
Shaman Pharmaceuticals, Inc., South San Francisco, California 94080-4812, USA.
Diabetologia. 1999 Jan;42(1):102-6. doi: 10.1007/s001250051121.
Extracts of the creosote bush (Larrea tridentata, family Zygophyllaceae) have long been used as a folk remedy for Type II (non-insulin-dependent) diabetes by native Americans in southwestern North America. In this study we have evaluated the metabolic effects of masoprocol, a pure compound isolated from the creosote bush, in a rat model of Type II diabetes. Animals were fed a 20% fat (by weight) diet for 2 weeks prior to intravenous injection with streptozotocin (STZ, 0.19 mmol/kg). Diabetic animals (glucose 16-33 mmol/l) were treated with vehicle, metformin (0.83 mmol/kg body weight) or masoprocol (0.83 mmol/kg body weight) twice a day for 4 days. Masoprocol treatment lowered glucose concentrations an average of 35% compared with vehicle (14.2+/-1.1 vs 21.7+/-1.0 mmol/l, p < 0.001), a reduction similar to metformin treatment (12.8+/-0.9 mmol/l), without any change in insulin concentration. Masoprocol treatment also lowered triglyceride concentrations 80% compared with vehicle (1.0+/-0.1 vs 4.8+/-0.3 mmol/l, p < 0.001), a reduction far greater than following metformin treatment (3.6+/-0.3 mmol/l). Non-esterified fatty acid and glycerol concentration were decreased by approximately 65% by masoprocol compared with vehicle, a reduction approximately twice as great as seen with metformin (p < 0.001). The effect of masoprocol on in vivo insulin-mediated glucose disposal was evaluated by infusing fat-fed/STZ rats with glucose (0.22 mmol kg x min(-1)) and insulin (30 pmol x kg x min(-1)) for 5 h. In response to the infusion, steady-state plasma glucose concentrations were reduced 30% in masoprocol-treated animals compared with vehicle controls (p < 0.05) with no change noted in rats treated with metformin. The effect of masoprocol treatment was also tested in primary adipocytes isolated from normal animals. Adipocytes treated with masoprocol (30 micromol/l) had higher basal and insulin-stimulated glucose clearance than did adipocytes treated with vehicle (p <0.05). These data show that masoprocol decreases both plasma glucose and triglyceride concentrations in fat-fed/STZ rats, presumably as a result of its ability to both increase glucose disposal and decrease lipolysis.
北美西南部的美洲原住民长期以来一直将石炭酸灌木（Larrea tridentata，蒺藜科）提取物用作II型（非胰岛素依赖型）糖尿病的民间疗法。在本研究中，我们评估了从石炭酸灌木中分离出的纯化合物马索罗酚在II型糖尿病大鼠模型中的代谢作用。在静脉注射链脲佐菌素（STZ，0.19 mmol/kg）前2周，给动物喂食20%（按重量计）脂肪饮食。糖尿病动物（血糖16 - 33 mmol/l）每天接受两次溶媒、二甲双胍（0.83 mmol/kg体重）或马索罗酚（0.83 mmol/kg体重）治疗，共4天。与溶媒相比，马索罗酚治疗使血糖浓度平均降低35%（14.2±1.1 vs 21.7±1.0 mmol/l，p<0.001），降低程度与二甲双胍治疗相似（12.8±0.9 mmol/l），胰岛素浓度无变化。与溶媒相比，马索罗酚治疗还使甘油三酯浓度降低80%（1.0±0.1 vs 4.8±0.3 mmol/l，p<0.001），降低幅度远大于二甲双胍治疗（3.6±0.3 mmol/l）。与溶媒相比，马索罗酚使非酯化脂肪酸和甘油浓度降低约65%，降低幅度约为二甲双胍的两倍（p<0.001）。通过给喂食脂肪/STZ大鼠输注葡萄糖（0.22 mmol·kg·min⁻¹）和胰岛素（30 pmol·kg·min⁻¹）5小时，评估马索罗酚对体内胰岛素介导的葡萄糖处置的影响。作为对输注的反应，与溶媒对照相比，马索罗酚治疗的动物稳态血浆葡萄糖浓度降低30%（p<0.05），二甲双胍治疗的大鼠无变化。还在从正常动物分离的原代脂肪细胞中测试了马索罗酚治疗的效果。用马索罗酚（30 μmol/l）处理的脂肪细胞比用溶媒处理的脂肪细胞具有更高的基础和胰岛素刺激的葡萄糖清除率（p<0.05）。这些数据表明，马索罗酚降低了喂食脂肪/STZ大鼠的血浆葡萄糖和甘油三酯浓度，推测是由于其增加葡萄糖处置和减少脂肪分解的能力。
