TY - JOUR
T1 - Interactions of captopril and verapamil on glucose tolerance and insulin action in an animal model of insulin resistance
AU - Dal Ponte, Donny B.
AU - Fogt, Donovan L.
AU - Jacob, Stephan
AU - Henriksen, Erik J.
N1 - Funding Information:
From the Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, AZ; and the Department of Endocrinology, Eberhard-Karls-University, Tiibingen, Germany. Submitted September 27, 1997; accepted February 9, 1998. Supported in part by Grant-in-Aid AZBG-24-95 from the Arizona Affiliate of the American Heart Association. Address reprint requests to Erik J. Henriksen, PhD, Department of Physiology, Ina E. Gittings Building #93, University of Arizona, Tucson, AZ 85721-0093. Copyright © 1998 by !~EB. Saunders Company 0026-0495/98/4708-0016503.00/0
PY - 1998
Y1 - 1998
N2 - We have shown previously that the combination of a long-acting, non- sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor (trandolapril) and the Ca2+ channel blocker verapamil improve insulin- stimulated glucose transport in skeletal muscle of the obese Zucker rat, a model of insulin resistance, hyperinsulinemia, and dyslipidemia. In the present study, we investigated the interactions of chronic treatment (28 days) with verapamil (20 mg/kg) and a short-acting, sulfhydryl-containing ACE inhibitor (captopril, 50 mg/kg) in combination on insulinemia, lipidemia, glucose tolerance, and insulin action on skeletal muscle glucose transport (2-deoxyglucose uptake in epitrochlearis) in lean and obese Zucker rats. In lean animals, verapamil alone and in combination with captopril actually increased (P < .05) plasma insulin, whereas in obese animals, verapamil alone worsened the hyperinsulinemia already present, and this effect was abolished by cotreatment with captopril. Captopril alone or in combination with verapamil reduced plasma free fatty acid (FFA) levels in obese rats, but not in lean rats. Captopril alone reduced the glucose-insulin index in obese animals given an oral glucose load, and this was associated with a significant increase in insulin-mediated muscle glucose transport. The greatest improvement in these responses was elicited in obese animals receiving combined captopril and verapamil treatment, and was associated with increases in muscle GLUT-4 glucose transporter protein and hexokinase and citrate synthase activities. In conclusion, these findings indicate that the short-acting, sulfhydryl-containing ACE inhibitor captopril can elicit beneficial metabolic effects on the hyperinsulinemia, dyslipidemia, glucose intolerance, and insulin resistance of muscle glucose transport of the obese Zucker rat. Moreover, there is a positive interactive effect on these pathophysiological parameters between captopril and verapamil in this animal model of insulin resistance.
AB - We have shown previously that the combination of a long-acting, non- sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor (trandolapril) and the Ca2+ channel blocker verapamil improve insulin- stimulated glucose transport in skeletal muscle of the obese Zucker rat, a model of insulin resistance, hyperinsulinemia, and dyslipidemia. In the present study, we investigated the interactions of chronic treatment (28 days) with verapamil (20 mg/kg) and a short-acting, sulfhydryl-containing ACE inhibitor (captopril, 50 mg/kg) in combination on insulinemia, lipidemia, glucose tolerance, and insulin action on skeletal muscle glucose transport (2-deoxyglucose uptake in epitrochlearis) in lean and obese Zucker rats. In lean animals, verapamil alone and in combination with captopril actually increased (P < .05) plasma insulin, whereas in obese animals, verapamil alone worsened the hyperinsulinemia already present, and this effect was abolished by cotreatment with captopril. Captopril alone or in combination with verapamil reduced plasma free fatty acid (FFA) levels in obese rats, but not in lean rats. Captopril alone reduced the glucose-insulin index in obese animals given an oral glucose load, and this was associated with a significant increase in insulin-mediated muscle glucose transport. The greatest improvement in these responses was elicited in obese animals receiving combined captopril and verapamil treatment, and was associated with increases in muscle GLUT-4 glucose transporter protein and hexokinase and citrate synthase activities. In conclusion, these findings indicate that the short-acting, sulfhydryl-containing ACE inhibitor captopril can elicit beneficial metabolic effects on the hyperinsulinemia, dyslipidemia, glucose intolerance, and insulin resistance of muscle glucose transport of the obese Zucker rat. Moreover, there is a positive interactive effect on these pathophysiological parameters between captopril and verapamil in this animal model of insulin resistance.
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U2 - 10.1016/S0026-0495(98)90355-9
DO - 10.1016/S0026-0495(98)90355-9
M3 - Article
C2 - 9711996
AN - SCOPUS:0031928230
VL - 47
SP - 982
EP - 987
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 8
ER -