MAZINDOL ENHANCES GLUCOSE-UPTAKE BY RAT SKELETAL-MUSCLE

The pharmacological action of mazindol rophenyl-2,3-dihydro-5-imidazo[ 2,1-alpha]isoindol) was examined by studying its effect on glucose upt ake by rat tissues using radiolabelled 2-deoxy-D-glucose. The followin g results were obtained. (1) The rate constant (K-i) of net tissue 2-d eoxy-D-glucose uptake increased in the cerebral cortex (4.7-fold, P < 0.05), the hypothalamus (4.6-fold, P < 0.05), heart (4.0 fold, P < 0.0 5) and skeletal muscles (gastrocnemius, 5.7-fold, P < 0.01; soleus, 4. 7-fold, P < 0.05), but not in epididymal adipose tissue in vivo 90 min after intragastric administration of mazindol (20 mg/kg). (2) This in crease in K-i values of net tissue 2-deoxy-D-glucose uptake was not ob served after addition of mazindol to the diet (40 mg/100 g of diet) fo r 4 days. (3) Mazindol (16.7 ng/ml to 16.7 mu g/ml) stimulated 2-deoxy -D-glucose transport into sarcolemmal vesicles of the gastrocnemius mu scle in vitro (1.6-1.8-fold, P < 0.05) and this stimulation was blocke d by cytochalasin B (10 mu M). These findings suggest that mazindol st imulates glucose transport into skeletal muscles by acting on glucose transporters in the sarcolemmal membrane, and suggest that mazindol ma y stimulate glucose transport into the brain and heart by a similar me chanism.