The effect of nitric oxide synthase inhibitor on improved insulin action by pioglitazone in high-fructose-fed rats.
The present study was performed to investigate whether nitric oxide synthase (NOS) inhibition influences the increased whole-body insulin action by pioglitazone in high-fructose-fed rats. Male Wistar rats aged 6 weeks were randomly divided into 3 groups and each group was fed one of the following diets for 3 weeks: standard chow diet (control group), high-fructose diet (fructose-fed group), and high-fructose diet plus pioglitazone (pioglitazone-treated group). The control and pioglitazone-treated groups were further divided into 2 subgroups respectively, and some rats of each subgroup were infused the NOS inhibitor, N(G)-monomethyl-l-arginine (L-NMMA), during the euglycemic clamp studies. In vivo insulin action was determined by the 2-step (3 and 30 mU/kg body weight [BW]/min low- and high-dose, respectively) hyperinsulinemic euglycemic clamp procedure in the awake condition. Glucose infusion rate (GIR) was considered as the index of insulin action. Endothelium-type NOS (eNOS) and inducible NOS (iNOS) in skeletal muscle were also measured. At the low-dose clamp, high-fructose feeding produced a marked decrease in GIR compared with the control group. Pioglitazone-treated animals showed a significant increase in GIR, reaching a similar level as the control group. However, the improved GIR was decreased to the level of the fructose-fed group by L-NMMA infusion. The GIR of the control group was not affected by L-NMMA infusion. The same tendency as the low-dose clamp was found at the high-dose clamp. In skeletal muscle, eNOS and iNOS protein content were not affected by high-fructose feeding and/or pioglitazone treatment. These results suggest that NOS inhibition can decrease the improved insulin resistance by pioglitazone in high-fructose-fed rats. Therefore, although NOS protein content is not changed by high-fructose feeding and/or pioglitazone treatment, it could be concluded that nitric oxide (NO) plays an important role in the improvement of insulin action by pioglitazone.
Koshinaka
K
K
Department of Sports Medicine, Graduate School of Medicine and the Research Center of Health, Physical Fitness and Sports, Nagoya University, Japan.
Oshida
Y
Y
Han
Y-Q
YQ
Ohsawa
I
I
Sato
Y
Y
D000818:Animals; D001835:Body Weight; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005632:Fructose / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004040:Dietary Carbohydrates; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D019323:omega-N-Methylarginine; D005632:Fructose; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D005947:Glucose; D000077205:Pioglitazone