Henriksen E J, Jacob S, Kinnick T R, Youngblood E B, Schmit M B, Dietze G J
Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona 85721-0093, USA.
Am J Physiol. 1999 Jul;277(1):R332-6. doi: 10.1152/ajpregu.1999.277.1.R332.
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 micrograms/kg ip), or the ANG II receptor (AT(1) 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-B(2) receptor antagonist HOE 140 (200 micrograms/kg ip) or the nitric oxide synthase inhibitor N(omega)-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 B(2) receptors and by an increase in nitric oxide production and/or action in skeletal muscle tissue.
急性给予血管紧张素转换酶（ACE）抑制剂卡托普利可增强胰岛素抵抗的肥胖Zucker大鼠骨骼肌中胰岛素刺激的葡萄糖转运活性。本研究旨在评估这种作用是由九肽缓激肽（BK）增加、血管紧张素II（ANG II）作用减弱还是两者共同介导的。肥胖Zucker大鼠（8 - 9周龄）分别用卡托普利（50 mg/kg口服）、缓激肽（200微克/千克腹腔注射）或ANG II受体（AT(1)亚型）拮抗剂依普罗沙坦（20 mg/kg口服）处理2小时。卡托普利处理使体外胰岛素刺激（2 mU/ml）的肱三头肌中2-脱氧葡萄糖摄取增加22%（251±7对205±9 pmol·mg(-1)·20 min(-1)；P<0.05），而缓激肽处理使该指标增加18%（249±15对215±7 pmol·mg(-1)·20 min(-1)；P<0.05）。依普罗沙坦未显著改变胰岛素作用。用特异性BK - B(2)受体拮抗剂HOE 140（200微克/千克腹腔注射）或一氧化氮合酶抑制剂N(ω)-硝基-L-精氨酸甲酯（50 mg/kg腹腔注射）预处理可完全消除BK介导的胰岛素作用增强。总体而言，这些结果表明BK对胰岛素作用的调节可能是ACE抑制剂在胰岛素抵抗的肥胖Zucker大鼠中产生代谢效应的基础。此外，BK对胰岛素作用的这种调节可能是通过B(2)受体以及骨骼肌组织中一氧化氮生成和/或作用的增加介导的。
