Liraglutide Prevents Hypoadiponectinemia-Induced Insulin Resistance and Alterations of Gene Expression Involved in Glucose and Lipid Metabolism
Liraglutide Prevents Hypoadiponectinemia-Induced Insulin Resistance and Alterations of Gene Expression Involved in Glucose and Lipid Metabolism
复制标题
DOI：
10.2119/molmed.2011.00051
复制
发表时间：
2011-11-01
影响因子：
5.7
通讯作者：
Yang, Gangyi
中科院分区：
文献类型：
--
作者：
Li, Ling;Miao, Zongyu;Yang, Gangyi
利拉鲁肽是一种胰高血糖素样肽(GLP)-1类似物，可降低血糖水平，增加胰岛素分泌，并通过尚未完全了解的机制改善胰岛素敏感性。因此，我们旨在评估利拉鲁肽在低脂联素血症和高脂肪饮食（HFD）诱导的胰岛素抵抗（IR）模型中的代谢影响和潜在机制。脂联素基因靶向使用腺病毒转导的RNAi实现，并用于降低血浆脂联素水平。利拉鲁肽（1 mg/kg）每日2次，连续8周给予hfd喂养的载脂蛋白（Apo）E-/-小鼠。胰岛素敏感性通过高胰岛素-正糖钳检查。采用实时荧光定量聚合酶链反应（PCR）和Western blot分别检测基因mRNA和蛋白的表达。利拉鲁肽可预防低脂联素血症引起的血浆胰岛素、游离脂肪酸、甘油三酯和总胆固醇升高。利拉鲁肽还能减轻低脂联素血症引起的外周和肝脏胰岛素敏感性的恶化以及涉及糖脂代谢的关键调节因子的改变。这些发现首次证明利拉鲁肽可以通过调节糖脂代谢相关基因和蛋白的表达来挽救低脂联素血症和HFD诱导的IR。(C) 2011范斯坦医学研究所，www.feinsteininstitute.org在线地址：http://www.molmed.org doi: 10.2119/molmed.2011.00051
Liraglutide is a glucagonlike peptide (GLP)-1 analog that reduces blood glucose levels, increases insulin secretion and improves insulin sensitivity through mechanisms that are not completely understood. Therefore, we aimed to evaluate the metabolic impact and underlying mechanisms of liraglutide in a hypoadiponectinemia and high-fat diet (HFD)-induced insulin resistance (IR) model. Adiponectin gene targeting was achieved using adenovirus-transduced RNAi and was used to lower plasma adiponectin levels. Liraglutide (1 mg/kg) was given twice daily for 8 wks to HFD-fed apolipoprotein (Apo)E-/- mice. Insulin sensitivity was examined by a hyperinsulinemic-euglycemic clamp. Gene mRNA and protein expressions were measured by quantitative real-time polymerase chain reaction (PCR) and Western blot, respectively. Administration of liraglutide prevented hypoadiponectinemia-induced increases in plasma insulin, free fatty acids, triglycerides and total cholesterol. Liraglutide also attenuated hypoadiponectinemia-induced deterioration in peripheral and hepatic insulin sensitivity and alterations in key regulatory factors implicated in glucose and lipid metabolism. These findings demonstrated for the first time that liraglutide could be used to rescue IR induced by hypoadiponectinemia and HFD via regulating gene and protein expression involved in glucose and lipid metabolism. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00051