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 (approximately 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 (approximately 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 micrograms/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.
Henriksen
E J
EJ
Department of Exercise and Sport Sciences, University of Arizona, Tucson 85721.
Jacob
S
S
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011924:Rats, Zucker
D007328:Insulin; D002216:Captopril; D005947:Glucose