Fabre Nelly T, Thieme Karina, Silva Karolline S, Catanozi Sérgio, Cavaleiro Ana Mercedes, Pinto Danilo A C, Okamoto Maristela M, Morais Mychel Raony P T, Falquetto Bárbara, Zorn Telma M, Machado Ubiratan F, Passarelli Marisa, Correa-Giannella Maria Lúcia
Laboratório de Carboidratos e Radioimunoensaios (Laboratório de Investigações Médicas, LIM-18), Faculdade de Medicina, Universidade de São Paulo (FMUSP), Brazil.
Laboratório de Lípides (Laboratório de Investigações Médicas, LIM-10), FMUSP, Brazil.
Mol Cell Endocrinol. 2017 May 15;447:116-124. doi: 10.1016/j.mce.2017.02.035. Epub 2017 Feb 24.
Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes. Additionally there was reduction in hepatic fat content, in expression of lipogenic, pro-inflamatory and pro-oxidative genes and increase in reactive oxygen species and in nuclear expression of NRF2, a transcription factor essential to cytoprotective response. Although considered toxic, AGEs become protective when administered chronically, stimulating AKT signaling, which is involved in cellular defense and insulin sensitivity.
由于关于晚期糖基化终产物（AGEs）对肝脏代谢影响的信息匮乏，我们评估了长期给予AGEs对以下方面的影响：（1）胰岛素敏感性；（2）参与AGEs、葡萄糖和脂肪代谢、氧化应激及炎症相关基因的肝脏表达；以及（3）肝脏形态和糖原含量。大鼠腹腔注射经晚期糖基化修饰或未修饰的白蛋白（AlbAGE），持续12周。AlbAGE诱导全身胰岛素抵抗的同时，肝脏胰岛素敏感性增加，表现为AKT激活、GSK3失活、肝脏糖原含量增加以及糖异生基因表达降低。此外，肝脏脂肪含量减少，脂肪生成、促炎和促氧化基因的表达降低，活性氧增加，NRF2（细胞保护反应所必需的转录因子）的核表达增加。尽管AGEs被认为具有毒性，但长期给药时它们具有保护作用，可刺激参与细胞防御和胰岛素敏感性的AKT信号传导。
