d-Fenfluramine improves hepatic insulin action in streptozotocin-diabetic rats.
We have examined the effect of chronic (21 days) oral administration of the serotoninergic anorectic drug d-fenfluramine (5 mg/kg) in a rat model of non-insulin-dependent diabetes (without obesity), as induced by injection of a low dose (45 mg/kg) of streptozotocin at 6 weeks, and characterized by marked hyperglycaemia and hepatic and peripheral insulin resistance. The following parameters were assessed: (1) basal blood glucose and insulin levels, and (2) basal and insulin-stimulated in vivo glucose production and glucose utilization, using the insulin-clamp technique in conjunction with isotopic measurement of glucose turnover. In the d-fenfluramine-treated diabetic rats, postabsorptive basal plasma glucose levels were decreased (7.8 +/- 0.3 mM as compared to 14.9 +/- 0.1 mM in the untreated diabetic rats) while the basal plasma insulin levels were unchanged. A similar reduction of the basal plasma glucose levels was observed in the pair-fed untreated diabetic group (8.3 +/- 0.2 mM). Basal glucose turnover was reduced by 45% (P < 0.01) in the d-fenfluramine-treated diabetic rats as well as in the pair-fed untreated diabetic rats. The impaired suppression of hepatic glucose output by insulin, caused by diabetes, was totally reversed by d-fenfluramine, while pair-feeding did not modify hepatic insulin resistance. The whole body insulin-mediated glucose uptake in the diabetic rats was also significantly improved by d-fenfluramine treatment. Such an effect was also found in the pair-fed untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Lab. Physiopathology of Nutrition, CNRS URA 307, Université D. Diderot, Paris, France.
F
F
Picarel-Blanchot
D
D
Bailbé
B
B
Portha
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D005277:Fenfluramine