METABOLIC DERANGEMENTS IN EXCESSIVE INSULIN AND SULFONYLUREA THERAPY

Mild streptozotocin diabetic rats, characterized by normal or slighty elevated fasting blood glucose levels and glucose intolerance, treated with excessive doses of monocomponent pork insulin (0.5 U/day) (I) or glybenclamide (0.6 mg/day) (S) were compared to controls (C) and stre ptozotocin-diabetic rats without treatment (D). Intravenous glucose to lerance tests (0.75 g/kg) were performed in all animals and repeated a fter overtreatment. Insulin binding and insulin-induced D-(U-C-14)-glu cose transport and oxidation were also determined in isolated epididym al adipocytes. Diabetic rats showed a failure in the initial phase of insulin release and glucose intolerance as compared with (C). In overt reated rats glucose tolerance worsened (p < 0.05) after therapy. Maxim al insulin binding by isolated adipocytes at tracer insulin concentrat ion was unchanged after excessive insulin or sulfonylurea therapy. Bes ides, glucose transport and oxidation in the cells of overtreated rats were greater than in D and even greater than in C. These apparently d ivergent results, i.e. deterioration of glucose tolerance with increas ed insulin action in adipocytes suggest that overtreatment induces a s tate of resistance to hormone action in other target tissue(s) than th e adipose one, possibly muscle.