Marti L, Abella A, Carpéné C, Palacín M, Testar X, Zorzano A
Departament de Bioquìmica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Diabetes. 2001 Sep;50(9):2061-8. doi: 10.2337/diabetes.50.9.2061.
Semicarbazide-sensitive amine oxidase (SSAO) is highly expressed in adipose cells, and substrates of SSAO, such as benzylamine, in combination with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 recruitment in 3T3-L1 and rat adipocytes. Here we examined whether acute and chronic administration of benzylamine and vanadate in vivo enhances glucose tolerance and reduces hyperglycemia in diabetic rats. Acute intravenous administration of these drugs enhanced glucose tolerance in nondiabetic rats and in streptozotocin (STZ)-induced diabetic rats. This occurred in the absence of changes in plasma insulin concentrations. However, the administration of benzylamine or vanadate alone did not improve glucose tolerance. The improvement caused by benzylamine plus vanadate was abolished when rats were pretreated with the SSAO-inhibitor semicarbazide. Chronic administration of benzylamine and vanadate exerted potent antidiabetic effects in STZ-induced diabetic rats. Although daily administration of vanadate alone (50 and 25 micromol x kg(-1) x day(-1) i.p.) for 2 weeks had little or no effect on glycemia, vanadate plus benzylamine reduced hyperglycemia in diabetic rats, enhanced basal and insulin-stimulated glucose transport, and upregulated GLUT4 expression in isolated adipocytes. In all, our results substantiated that acute and chronic administration of benzylamine with low dosages of vanadate have potent antidiabetic effects in rats.
氨基脲敏感胺氧化酶（SSAO）在脂肪细胞中高度表达，SSAO的底物，如苄胺，与低浓度的钒酸盐联合使用时，能强烈刺激3T3-L1细胞和大鼠脂肪细胞中的葡萄糖转运及葡萄糖转运蛋白4（GLUT4）的募集。在此，我们研究了体内急性和慢性给予苄胺和钒酸盐是否能增强糖尿病大鼠的葡萄糖耐量并降低高血糖。急性静脉注射这些药物可增强非糖尿病大鼠和链脲佐菌素（STZ）诱导的糖尿病大鼠的葡萄糖耐量。这一现象发生时血浆胰岛素浓度并无变化。然而，单独给予苄胺或钒酸盐并不能改善葡萄糖耐量。当用SSAO抑制剂氨基脲预处理大鼠后，苄胺加钒酸盐所引起的葡萄糖耐量改善作用被消除。慢性给予苄胺和钒酸盐对STZ诱导的糖尿病大鼠具有显著的抗糖尿病作用。尽管单独每日腹腔注射钒酸盐（50和25 μmol·kg⁻¹·天⁻¹）2周对血糖几乎没有影响，但钒酸盐加苄胺可降低糖尿病大鼠的高血糖，增强基础状态及胰岛素刺激的葡萄糖转运，并上调分离脂肪细胞中GLUT4的表达。总之，我们的结果证实，急性和慢性给予低剂量钒酸盐的苄胺对大鼠具有显著的抗糖尿病作用。
