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.min(-1)) and insulin (30 pmol.kg.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 mu mol/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.