Metabolic derangements in excessive insulin and sulfonylurea therapy.
Mild streptozotocin diabetic rats, characterized by normal or slightly 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 streptozotocin-diabetic rats without treatment (D). Intravenous glucose tolerance tests (0.75 g/kg) were performed in all animals and repeated after overtreatment. Insulin binding and insulin-induced D-(U-14C)-glucose transport and oxidation were also determined in isolated epididymal adipocytes. Diabetic rats showed a failure in the initial phase of insulin release and glucose intolerance as compared with (C). In overtreated rats glucose tolerance worsened (p < 0.05) after therapy. Maximal insulin binding by isolated adipocytes at tracer insulin concentration was unchanged after excessive insulin or sulfonylurea therapy. Besides, glucose transport and oxidation in the cells of overtreated rats were greater than in D and even greater than in C. These apparently divergent results, i.e. deterioration of glucose tolerance with increased insulin action in adipocytes suggest that overtreatment induces a state of resistance to hormone action in other target tissue(s) than the adipose one, possibly muscle.
Ursich
M J
MJ
Laboratory of Medical Investigation (LIM 18), Hospital das Clinicas, University of São Paulo Medical School, Brazil.
Fukui
R T
RT
Rocha
D M
DM
Silva
M E
ME
Wajchenberg
B L
BL
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D013552:Swine
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D013453:Sulfonylurea Compounds