THE EFFECTS OF MAZINDOL AND 46-034 (SANDOZ) ON GLUCOSE OXIDATION AND INSULIN BINDING BY RAT ISOLATED FAT CELLS

1. The anorexic agent mazindol and its major metabolite 46-034 (Sandoz) in high concentrations (>0·4 mM) abolished basal and insulin-stimulated conversion of 1-¹⁴C-glucose to ¹⁴CO₂ by rat isolated fat cells. 2. High concentrations (1 mM) also inhibited specific binding of ¹²⁵I-insulin to fat cells. 3. The observed effects appeared to be due in part to perturbation of the plasma membrane since there was a rise in the lactate dehydrogenase content of the incubation medium, increased ¹²⁵I-insulin degradation and a reduction in cellular tritiated water space. 4. These effects are unlikely to be relevant to the therapeutic action of mazindol.