TY - JOUR
T1 - Glucose transport activity in insulin-resistant rat muscle
T2 - Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism
AU - Henriksen, E. J.
AU - Jacob, S.
AU - Augustin, H. J.
AU - Dietze, G. J.
PY - 1996
Y1 - 1996
N2 - Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis of NIDDM and is associated with hypertension, obesity, and dyslipidemia. Angiotensin-converting enzyme (ACE) inhibitors are used primarily in antihypertensive therapy but also are known to improve whole- body insulin-mediated glucose disposal. However, the exact site of action is not well characterized. We have used the isolated epitrochlearis muscle from a well-established animal model of skeletal muscle insulin resistance, the obese Zucker rat, to test the effect of oral administration of ACE inhibitors on insulin-sensitive muscle glucose transport activity. Both acute and chronic administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non-sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in vitro insulin-mediated muscle glucose transport activity. In addition, the acute effect of oral captopril administration was completely abolished by pretreatment of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings indicate that ACE inhibitors may improve whole-body glucose metabolism by acting on the insulin-sensitive skeletal muscle glucose transport system. In addition, bradykinin or one of its metabolites may be involved in the action of the ACE inhibitor captopril on insulin-resistant muscle.
AB - Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis of NIDDM and is associated with hypertension, obesity, and dyslipidemia. Angiotensin-converting enzyme (ACE) inhibitors are used primarily in antihypertensive therapy but also are known to improve whole- body insulin-mediated glucose disposal. However, the exact site of action is not well characterized. We have used the isolated epitrochlearis muscle from a well-established animal model of skeletal muscle insulin resistance, the obese Zucker rat, to test the effect of oral administration of ACE inhibitors on insulin-sensitive muscle glucose transport activity. Both acute and chronic administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non-sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in vitro insulin-mediated muscle glucose transport activity. In addition, the acute effect of oral captopril administration was completely abolished by pretreatment of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings indicate that ACE inhibitors may improve whole-body glucose metabolism by acting on the insulin-sensitive skeletal muscle glucose transport system. In addition, bradykinin or one of its metabolites may be involved in the action of the ACE inhibitor captopril on insulin-resistant muscle.
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U2 - 10.2337/diab.45.1.s125
DO - 10.2337/diab.45.1.s125
M3 - Article
C2 - 8529793
AN - SCOPUS:0030032963
SN - 0012-1797
VL - 45
SP - S125-S128
JO - Diabetes
JF - Diabetes
IS - 1 SUPPL.
ER -