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.