In addition to their hypotensive action, angiotensin-converting enzyme (ACE) inhibitors exert a beneficial effect on glucoregulation. In the present study, the effect of ACE inhibition by captopril on glucose utilization in peripheral tissues was investigated in non-obese rats with hereditary hypertriglyceridemia (HHTg) associated with hyperinsulinemia and insulin resistance. Normotriglyceridemic Wistar rats served as controls (C). Rats of both groups received a high-sucrose diet, and a half of each group also captopril in drinking water (10 mg/kg body weight [bw]) for 2 weeks. Captopril administration reduced fasting glycemia and postprandial triglyceridemia in HHTg rats, while the fasting levels of nonesterified fatty acids (NEFA), glycerol, and lactate were decreased in both groups. The sensitivity of skeletal muscle to insulin action evaluated as in vitro 14C-glucose incorporation into glycogen was significantly increased by captopril treatment both in HHTg (3.51 +/- 0.48 v 2.0 +/- 0.12 micromol glucose/g wet weight [ww]) and C (3.32 +/- 0.21 v 2.48 +/- 0.09 micromol glucose/g ww). In isolated adipose tissue, the insulin-stimulated 14C-glucose incorporation into neutral lipids was increased, after captopril administration, by 137% in C and by 35% only in HHTg. After captopril treatment, insulin-stimulated de novo fatty acid synthesis rose significantly in C while remaining low in HHTg. The increase in esterification was comparable in both groups. Separate experiments were designed to assess the possible involvement of bradykinin in mediating captopril action. Both C and HHTg rats fed a high-sucrose diet for 2 weeks were treated with captopril (50 mg/kg orally) for 1 hour; half of each group received the specific inhibitor of bradykinin receptor HOE-140 (100 microg/kg intraperitoneally [i.p.]) 1 hour before captopril administration. In C, captopril administration enhanced the insulin-stimulated in vitro glucose incorporation into lipids in adipose tissue by 255%, and into glycogen in the musculus soleus by 45%; this effect was eliminated by HOE-140. In HHTg, neither a single dose of captopril nor HOE-140 had any effect. We conclude that long-term captopril administration increased the insulin sensitivity of peripheral tissue in both C and HHTg rats, but with different efficacy. While the insulin-sensitizing action of captopril on skeletal muscle was comparable in HHTg and C rats, there were differences in the effect of captopril on adipose tissue. The difference became particularly manifest in de novo fatty acid synthesis.

Department of Metabolic Research Institute for Clinical and Experimental Medicine Prague Czech Republic

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