Effects of imidapril, an angiotensin-converting enzyme inhibitor, on insulin sensitivity and responsiveness in streptozotocin-induced diabetic rats.
We have studied the effect of imidapril, an angiotensin-converting enzyme inhibitor, on streptozotocin-induced diabetic rats. A sequential euglycemic hyperinsulinemic clamp procedure was used (insulin infusion rates: 3 and 30 mU/kg BW/min) in 30 diabetic rats. The rats were divided in 6 groups: a control group, a control group with N-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min, a nitric oxide synthase inhibitor) infusion, a streptozotocin-induced diabetic group, a diabetic group with L-NMMA infusion, a diabetic group involving imidapril infusion (5 microg/kg/min), and a diabetic group involving simultaneous imidapril and L-NMMA infusion. Glucose concentrations were maintained around 140 mg/dl during the clamp studies. Plasma insulin levels during the 3 and 30 mU/kg BW/min insulin infusions were 30 and 400 microU/ml, respectively. Glucose infusion rates (GIR) in STZ-induced diabetic rats showed a significant decrease compared to controls. At both insulin infusion rates, imidapril-infused diabetic rats showed an increased GIR, compared with the saline infused ones. There was no significant difference in GIR between L-NMMA and saline infusion in diabetic rats. Simultaneous infusion of imidapril and L-NMMA did not significantly decrease GIR with low-dose insulin infusion, but the increase in GIR induced by imidapril with high-dose insulin infusion was impaired by 100 % by L-NMMA infusion in diabetic rats. These results suggest that imidapril may improve insulin action, in part, via nitric oxide.
Viana
A Y I
AY
Department of Sports Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Oshida
Y
Y
Han
Y-Q
YQ
Koshinaka
K
K
Sato
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D048289:Imidazolidines; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D007328:Insulin; D019323:omega-N-Methylarginine; C065166:imidapril; D019001:Nitric Oxide Synthase; D005947:Glucose