Morin Nathalie, Visentin Virgile, Calise Denis, Marti Luc, Zorzano Antonio, Testar Xavier, Valet Philippe, Fischer Yvan, Carpéné Christian
Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
J Pharmacol Exp Ther. 2002 Dec;303(3):1238-47. doi: 10.1124/jpet.102.040592.
Tyramine and benzylamine have been described as stimulators of glucose transport in adipocytes. This effect is dependent on amine oxidation by monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO) and on the subsequent hydrogen peroxide formation as already demonstrated by blockade with oxidase inhibitors or antioxidants and potentiation with vanadate. In this work, we extended these observations to skeletal muscle and cardiac myocytes using in vitro and in vivo approaches. Tissue distribution studies showed that substantial extrahepatic peripheral MAO activities exist in kidney and gut, but also in insulin-sensitive tissues: heart, adipose tissue, and skeletal muscles. SSAO activity is also widely distributed and present at a lower level than MAO, except in fat depots where both oxidases were equally involved in tyramine oxidation. When tested in vitro at millimolar doses, tyramine caused a large stimulation of glucose transport in rat adipocytes and in skeletal and cardiac muscles. In vivo administration of tyramine (4 mg/kg i.p.) lowered the hyperglycemic responses to a glucose challenge in control and in streptozotocin-treated rats. This positive effect on glucose disposal was obtained without vanadate and was abolished by SSAO and MAO inhibitors. Tyramine increased hexose uptake in vivo in insulin-sensitive tissues, whereas it induced only transient effects on plasma insulin or cardiovascular parameters. In conclusion, activation of the amine oxidases present in insulin-sensitive tissues induces insulin-like effects, readily detectable in vitro, and increasing peripheral glucose utilization in vivo.
酪胺和苄胺已被描述为脂肪细胞中葡萄糖转运的刺激剂。这种作用依赖于单胺氧化酶（MAO）或氨基脲敏感胺氧化酶（SSAO）对胺的氧化作用以及随后的过氧化氢生成，这已通过氧化酶抑制剂或抗氧化剂的阻断以及钒酸盐的增强作用得到证实。在这项研究中，我们使用体外和体内方法将这些观察结果扩展到骨骼肌和心肌细胞。组织分布研究表明，肾和肠道中存在大量肝外外周MAO活性，胰岛素敏感组织如心脏、脂肪组织和骨骼肌中也存在。SSAO活性也广泛分布，且水平低于MAO，除了在脂肪库中两种氧化酶在酪胺氧化中起同等作用。当以毫摩尔剂量在体外进行测试时，酪胺可显著刺激大鼠脂肪细胞以及骨骼肌和心肌中的葡萄糖转运。体内给予酪胺（4 mg/kg腹腔注射）可降低对照大鼠和链脲佐菌素处理大鼠对葡萄糖刺激的高血糖反应。这种对葡萄糖处置的积极作用在没有钒酸盐的情况下即可获得，并且被SSAO和MAO抑制剂消除。酪胺可增加胰岛素敏感组织中体内己糖摄取，而对血浆胰岛素或心血管参数仅产生短暂影响。总之，胰岛素敏感组织中存在的胺氧化酶的激活会诱导胰岛素样作用，在体外易于检测到，并增加体内外周葡萄糖利用。
