Effect of masoprocol on carbohydrate and lipid metabolism in a rat model of Type II diabetes.

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.