Caperuto Luciana C, Anhê Gabriel F, Amanso Angélica M, Ribeiro Luciene M, Medina Mayrin C, Souza Lilian C, Carvalho Olga M F, Bordin Silvana, Saad Mário J A, Carvalho Carla R O
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brasil.
Endocrine. 2006 Jun;29(3):391-8. doi: 10.1385/ENDO:29:3:391.
In the present study, we investigated the protein levels and phosphorylation status of the insulin receptor and insulin receptor substrates (IRS-1, IRS-2, and IRS-3) as well as their association with PI(3)-kinase in the rat adipose tissue of two models of insulin resistance: dexamethasone treatment and aging. AKT and atypical PKC phosphorylation detection were also performed. Both models showed decreased insulin-induced IRS-1 and IRS-2 tyrosine phosphorylation, accompanied by reduced protein levels of IRS-1 and IRS-2. Nevertheless, IRS-3 protein level was unchanged in aging but increased in dexamethasone-treated rats. PI(3)-kinase association with IRS-1 was reduced in aged rats, whereas dexamethasone-treated rats showed a reduced IRS-2/ PI(3)-kinase association. However, IRS-3 association with PI(3)-kinase was reduced in both models, as well as insulin-induced AKT and PKC phosphorylation. The alterations described in the present study show that the action of insulin is differently impaired depending on the origin of insulin resistance. These differences might be directly linked to the singular metabolic features of the models we tested.
在本研究中，我们调查了两种胰岛素抵抗模型（地塞米松处理和衰老）的大鼠脂肪组织中胰岛素受体及胰岛素受体底物（IRS-1、IRS-2和IRS-3）的蛋白水平和磷酸化状态，以及它们与PI(3)-激酶的关联。同时也进行了AKT和非典型PKC磷酸化检测。两种模型均显示胰岛素诱导的IRS-1和IRS-2酪氨酸磷酸化降低，同时IRS-1和IRS-2的蛋白水平也降低。然而，衰老大鼠中IRS-3蛋白水平未变，而地塞米松处理的大鼠中IRS-3蛋白水平升高。老年大鼠中PI(3)-激酶与IRS-1的关联降低，而地塞米松处理的大鼠中IRS-2/PI(3)-激酶的关联降低。然而，两种模型中IRS-3与PI(3)-激酶的关联均降低，以及胰岛素诱导的AKT和PKC磷酸化也降低。本研究中描述的这些改变表明，胰岛素的作用根据胰岛素抵抗的来源不同而受到不同程度的损害。这些差异可能与我们所测试模型的独特代谢特征直接相关。
