Zorzano Antonio, Abella Anna, Marti Luc, Carpéné Christian, Palacín Manuel, Testar Xavier
Facultat de Biologia, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, 08028 Barcelona, Spain.
Biochim Biophys Acta. 2003 Apr 11;1647(1-2):3-9. doi: 10.1016/s1570-9639(03)00039-6.
Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. Moreover, the acute administration of benzylamine and vanadate in vivo enhances glucose tolerance in non-diabetic and streptozotocin-induced diabetic rats and reduces hyperglycemia after chronic treatment in streptozotocin-diabetic rats. Based on these observations, we propose that SSAO activity and vanadate potently mimic insulin effects in adipose cells and exert an anti-diabetic action in an animal model of type 1 diabetes mellitus.
氨基脲敏感胺氧化酶（SSAO）在脂肪细胞的质膜中含量非常丰富。SSAO底物与低浓度钒酸盐的组合通过一种需要SSAO活性和过氧化氢形成的机制，显著刺激大鼠脂肪细胞中的葡萄糖转运以及GLUT4葡萄糖转运蛋白向细胞表面的募集。SSAO的底物如苄胺或酪胺与钒酸盐结合，可有效刺激脂肪细胞中胰岛素受体底物1（IRS-1）和3（IRS-3）的酪氨酸磷酸化以及磷脂酰肌醇3激酶（PI 3激酶）活性，这一过程发生在胰岛素受体激酶受到微弱刺激的情况下。此外，在体内急性给予苄胺和钒酸盐可提高非糖尿病和链脲佐菌素诱导的糖尿病大鼠的葡萄糖耐量，并降低链脲佐菌素糖尿病大鼠长期治疗后的高血糖。基于这些观察结果，我们提出SSAO活性和钒酸盐在脂肪细胞中可有效模拟胰岛素作用，并在1型糖尿病动物模型中发挥抗糖尿病作用。
