ACE inhibition and glucose transport in insulin-resistant muscle: Roles of bradykinin and nitric oxide

Erik J. Henriksen, Stephan Jacob, Tyson R. Kinnick, Erik B. Youngblood, Melanie B. Schmit, Guenther J. Dietze

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Acute administration of the angiotensin-converting enzyme (ACE) inhibitor captopril enhances insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat. The present study was designed to assess whether this effect is mediated by an increase in the nonapeptide bradykinin (BK), by a decrease in action of ANG II, or both. Obese Zucker rats (8-9 wk old) were treated for 2 h with either captopril (50 mg/kg orally), bradykinin (200 μg/kg ip), or the ANG II receptor (AT1 subtype) antagonist eprosartan (20 mg/kg orally). Captopril treatment enhanced in vitro insulin-stimulated (2 mU/ml) 2-deoxyglucose uptake in the epitrochlearis muscle by 22% (251 ± 7 vs. 205 ± 9 pmol · mg-1 · 20 min-1; P < 0.05), whereas BK treatment enhanced this variable by 18% (249 ± 15 vs. 215 ± 7 pmol · mg-1 · 20 min-1; P < 0.05). Eprosartan did not significantly modify insulin action. The BK-mediated increase in insulin action was completely abolished by pretreatment with either the specific BK- B2 receptor antagonist HOE 140 (200 μg/kg ip) or the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine methyl ester (50 mg/kg ip). Collectively, these results indicate that the modulation of insulin action by BK likely underlies the metabolic effects of ACE inhibitors in the insulin-resistant obese Zucker rat. Moreover, this modulation of insulin action by BK is likely mediated through B2 receptors and by an increase in nitric oxide production and/or action in skeletal muscle tissue.

Original languageEnglish (US)
Pages (from-to)R332-R336
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume277
Issue number1 46-1
DOIs
StatePublished - Jul 1999

Keywords

  • 2-deoxyglucose uptake
  • Epitrochlearis muscle
  • Obese Zucker rat

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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