TY - JOUR
T1 - Effects of captopril on glucose transport activity in skeletal muscle of obese Zucker rats
AU - Henriksen, Erik J.
AU - Jacob, Stephan
N1 - Funding Information:
From the Muscle Metabolism Laboratory, Department of Exercise and Sport Sciences, University of Arizona, Tucson, AZ; Forscher-gruppe Hypertonie und Diabetes, Biihlerh6he; and Stadtklinik-Baden, Baden, Germany. Submitted January 26, 1994; accepted April 7, 1994. Supported in part by a grant from Bristol-Myers Squibb, Munich, Germany, and Grunt-in-Aid No. AZG-3-93 from the Arizona AJfiliate of the American Heart Association. Address reprint requests to Erik J. Henriksen, PhD, Department of Exercise and Sport Sciences, Ina E. Gittings Building, Room 111, University of Arizona, Tucson, AZ85721. Copyright © 1995 by W.B. Saunders Company 0026-0495/95/4402-0023503.00/0
PY - 1995/2
Y1 - 1995/2
N2 - 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 (∼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 (∼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 μg/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.
AB - 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 (∼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 (∼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 μg/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.
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U2 - 10.1016/0026-0495(95)90276-7
DO - 10.1016/0026-0495(95)90276-7
M3 - Article
C2 - 7869926
AN - SCOPUS:0028931911
VL - 44
SP - 267
EP - 272
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 2
ER -