Liraglutide Prevents Hypoadiponectinemia-Induced Insulin Resistance and Alterations of Gene Expression Involved in Glucose and Lipid Metabolism
| Autor: | Gangyi Yang, Ling Li, Rui Liu, Mengliu Yang, Zongyu Miao, Hua Liu |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Apolipoprotein B Blotting Western Carbohydrate metabolism Real-Time Polymerase Chain Reaction Mice Insulin resistance Glucagon-Like Peptide 1 3T3-L1 Cells Hyperinsulinism Internal medicine Genetics medicine Animals Gene Silencing Molecular Biology Triglycerides Genetics (clinical) Glucose tolerance test biology medicine.diagnostic_test Adiponectin Chemistry Liraglutide Lipid metabolism Articles Glucose Tolerance Test Glucose clamp technique Lipid Metabolism medicine.disease Cholesterol Glucose Endocrinology Gene Expression Regulation Liver Gene Knockdown Techniques Glucose Clamp Technique biology.protein Molecular Medicine Insulin Resistance medicine.drug |
| Zdroj: | Molecular Medicine. 17:1168-1178 |
| ISSN: | 1528-3658 1076-1551 |
| DOI: | 10.2119/molmed.2011.00051 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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