Dietze G J, Wicklmayr M, Rett K, Jacob S, Henriksen E J
Third Medical Department, Schwabing Hospital, Munich, Germany.
Diabetes. 1996 Jan;45 Suppl 1:S110-4. doi: 10.2337/diab.45.1.s110.
Using the euglycemic-hyperinsulinemic glucose clamp and the human forearm technique, we have demonstrated that the improved glucose disposal rate observed after the administration of an angiotensin-converting enzyme (ACE) inhibitor such as captopril may be primarily due to increased muscle glucose uptake (MGU). These results are not surprising because ACE, which is identical to the bradykinin (BK)-degrading kininase II, is abundantly present in muscle tissue, and its inhibition has been observed to elicit the observed metabolic actions via elevated tissue concentrations of BK and through a BK B2 receptor site in muscle and/or endothelial tissue. These findings are supported by several previous studies. Exogenous BK applied into the brachial artery of the human forearm not only augmented muscle blood flow (MBF) but also enhanced the rate of MGU. In another investigation, during rhythmic voluntary contraction, both MBF and MGU increased in response to the higher energy expenditure, and the release of BK rose in the blood vessel, draining the working muscle tissue. Inhibition of the activity of the BK-generating protease in muscle tissue (kallikrein) with aprotinin significantly diminished these functional responses during contraction. Applying the same kallikrein inhibitor during the infusion of insulin into the brachial artery significantly reduced the effect of insulin on glucose uptake into forearm muscle. This is of interest, because in recent studies insulin has been suggested to elicit its actions on MBF and MGU via the accelerated release of endothelium-derived nitric oxide, the generation of which is also stimulated by BK in a concentration-dependent manner. This new evidence obtained from in vitro and in vivo studies sheds new light on the discussion of whether BK may play a role in energy metabolism of skeletal muscle tissue.
运用正常血糖-高胰岛素血糖钳夹技术和人体前臂技术，我们已证明，给予卡托普利等血管紧张素转换酶（ACE）抑制剂后观察到的葡萄糖处置率提高，可能主要归因于肌肉葡萄糖摄取（MGU）增加。这些结果并不令人惊讶，因为与缓激肽（BK）降解酶激肽释放酶II相同的ACE在肌肉组织中大量存在，并且已观察到其抑制作用可通过提高组织中BK的浓度以及通过肌肉和/或内皮组织中的BK B2受体位点引发观察到的代谢作用。这些发现得到了先前多项研究的支持。将外源性BK注入人体前臂的肱动脉，不仅增加了肌肉血流量（MBF），还提高了MGU速率。在另一项研究中，在有节奏的自主收缩过程中，MBF和MGU均因更高的能量消耗而增加，并且在引流工作肌肉组织的血管中BK的释放增加。用抑肽酶抑制肌肉组织中产生BK的蛋白酶（激肽释放酶）的活性，可显著减弱收缩过程中的这些功能反应。在向肱动脉输注胰岛素期间应用相同的激肽释放酶抑制剂，可显著降低胰岛素对前臂肌肉葡萄糖摄取的作用。这很有意思，因为在最近的研究中，有人提出胰岛素通过加速内皮衍生一氧化氮的释放来对MBF和MGU发挥作用，而BK也以浓度依赖的方式刺激一氧化氮的生成。从体外和体内研究获得的这一新证据为BK是否可能在骨骼肌组织的能量代谢中发挥作用的讨论提供了新的线索。
