Abstract
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 μg/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 μU/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.
Key words
Angiotensin-Converting Enzyme Inhibitor - Euglycemic Clamp Technique - L-NMMA - Streptozotocin
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Y. Sato, M. D, Ph. D.
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