Effect of imidapril, an angiotensin-converting enzyme inhibitor, on fructose-induced insulin resistance in rats.
The effect of imidapril, an angiotensin-converting enzyme (ACE) inhibitor, on insulin resistance was studied in high-fructose-fed rats. A sequential hyperinsulinemic euglycemic clamp procedure (insulin infusion rates: 3 and 30 mU/kg BW/min) was employed in 15 high-fructose-fed rats and 10 normal chow-fed rats under the awake condition. Five of the high-fructose-fed and five of the normal chow-fed rats, respectively, were continuously given imidapril (5 mg/kg BW/min) or saline during the two-step euglycemic clamp study. Furthermore, both imidapril and L-NMMA were infused in another 5 high-fructose-fed rats during the low-dose insulin clamp. Glucose infusion rate (GIR) was regarded as an index of the whole-body insulin action. In the low-dose insulin infusion, the high-fructose feeding resulted in a marked decrease in GIR (p<0.05). Imidapril infusion significantly raised the GIRs in the high-fructose-fed rats (p<0.05). There was no significant difference in GIRs between the chow-fed rats and the imidapril-infused rats with high-fructose diet. In the high-fructose-fed rats, L-NMMA abolished the increase in GIR induced by imidapril (p<0.05). Imidapril did not significantly change the GIRs in the chow-fed rats. In the high-dose insulin infusion, no significant difference in GIR was found among the chow-fed rats, the chow-fed rats given imidapril, the high-fructose-fed rats, and the high-fructose-fed rats given imidapril. These results suggest that, in insulin-resistant rats induced by the high-fructose feeding, an ACE inhibitor, such as imidapril, can improve the whole-body insulin-mediated glucose disposal and that this effect of imidapril is essentially linked to increased activation of NO-pathway.
Oda
Tsuneyuki
T
Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan.
Hirata
Masanobu
M
Oshida
Yoshiharu
Y
Han
Yan-Qing
YQ
Koshinaka
Keiichi
K
Sato
Yuzo
Y
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D015309:Glucose Clamp Technique; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D007328:Insulin; D019323:omega-N-Methylarginine; D005632:Fructose; C065166:imidapril; D019001:Nitric Oxide Synthase; D005947:Glucose