Liraglutide Prevents Hypoadiponectinemia-Induced Insulin Resistance and Alterations of Gene Expression Involved in Glucose and Lipid Metabolism
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.
This work was supported by grants from the National Natural Science Foundation of China (30871199, 30771037, 30971388 and 81070640) and the Doctoral Fund of Ministry of Education of China (20105503110002).
- 21.Yu C, Gangyi Y, Ling L, Ling K, Wenwen C. (2009) The changes of glucose-lipid metabolism in ApoE−/− mice with high-fat induced insulin resistance. Chinese J. Diabetes. 17:590–603.Google Scholar