INSERM, U858, Institut de Médecine Moléculaire de Rangueil, IFR 150, Toulouse, France.
Pharmacol Res. 2010 Apr;61(4):355-63. doi: 10.1016/j.phrs.2009.12.014. Epub 2010 Jan 4.
Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.
苯甲胺存在于辣木中,这种植物在传统医学中被用于治疗糖尿病。在哺乳动物中,苯甲胺被半脒基敏感胺氧化酶(SSAO)代谢为苯甲醛和过氧化氢。后者具有胰岛素模拟作用,并且参与了苯甲胺对人脂肪细胞的作用:刺激葡萄糖转运和抑制脂肪分解。本研究检查了慢性口服苯甲胺是否可以改善超重和糖尿病前期小鼠的葡萄糖耐量和循环脂质谱,而不会增加氧化应激。使用外翻肠囊验证了苯甲胺在肠道中的扩散。然后,在高脂肪饮食(HFD)喂养的胰岛素抵抗小鼠中测量了葡萄糖处理和代谢标志物,并在其饮用水中(3600μmol/(kg·天))接受或不接受苯甲胺 17 周。与 HFD 对照组相比,HFD-苯甲胺小鼠的体重增加、空腹血糖、总血浆胆固醇和高血糖负荷反应降低。在脂肪细胞中,胰岛素诱导的葡萄糖转运激活和脂肪分解抑制保持不变。在主动脉中,苯甲胺治疗部分恢复了 HFD 降低的亚硝酸盐水平。在肝脏中,脂质过氧化标志物减少。作为代谢综合征的替代血浆标志物的抵抗素和尿酸减少。尽管在胺氧化过程中产生的过氧化氢具有潜在的有害性质,并且与在脂肪细胞上发现的体外胰岛素样作用一致,但 SSAO 底物苯甲胺可被视为治疗代谢综合征的潜在口服药物。