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Molecular Medicine

, Volume 17, Issue 11–12, pp 1168–1178 | Cite as

Liraglutide Prevents Hypoadiponectinemia-Induced Insulin Resistance and Alterations of Gene Expression Involved in Glucose and Lipid Metabolism

  • Ling Li
  • Zongyu Miao
  • Rui Liu
  • Mengliu Yang
  • Hua Liu
  • Gangyi Yang
Research Article

Abstract

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.

Notes

Acknowledgments

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).

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Ling Li
    • 1
  • Zongyu Miao
    • 1
  • Rui Liu
    • 2
  • Mengliu Yang
    • 2
  • Hua Liu
    • 3
  • Gangyi Yang
    • 2
  1. 1.Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical BiochemistryChongqing Medical University College of Laboratory MedicineChongqingChina
  2. 2.Department of Endocrinology, the Second Affiliated HospitalChongqing Medical UniversityChongqingChina
  3. 3.Department of PediatricsUniversity of Mississippi Medical CenterJacksonUSA

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