EFFECTS OF CAPTOPRIL ON GLUCOSE-TRANSPORT ACTIVITY IN SKELETAL-MUSCLE OF OBESE ZUCKER RATS

This study tested whether the angiotensin-converting enzyme (ACE) inhibitor captopril can modify the glucose transport system in insulin-resistant skeletal muscle. Obese Zucker (fa/fa) rats (similar to 300 g)-a model of insulin resistance-were administered by gavage either a single dose (50 mg/kg body weight) or repeated doses (50 mg/kg/d for 14 consecutive days) of captopril. Corresponding groups of age-matched, vehicle-treated lean (Fa/-) littermates (similar to 170 g) were also studied. Glucose transport activity in the epitrochlearis muscle was assessed by in vitro 2-deoxyglucose (2-DG) uptake. The increase in 2-DG uptake due to insulin (2 mU/mL) in muscles from vehicle-treated obese rats was less than 50% (P < .05) of the increase observed in muscles from lean rats. Short-term captopril treatment improved insulin-stimulable 2-DG uptake in muscles from obese rats by 46% (P < .05), and this enhanced insulin action due to captopril was completely abolished by pretreatment with the bradykinin antagonist HOE 140 (100 mu g/kg). Long-term treatment with captopril produced a 60% improvement in insulin-stimulated 2-DG uptake (P < .05). Contraction-stimulated 2-DG uptake was significantly impaired (-31%, P < .05) in the obese rat, but was not altered by long-term captopril treatment. These findings indicate that both short- and long-term treatments with captopril significantly improve insulin-stimulated glucose transport activity in skeletal muscle of the obese Zucker rat, and that this improvement involves bradykinin metabolism, These data therefore support the hypothesis that captopril-induced improvements in glucose disposal result in part from an enhancement of the skeletal muscle glucose transport system. Copyright (C) 1995 by W.B. Saunders Company