Molecular medicine reports, 2018-05, Vol.17 (5), p.7372-7380
2018
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- Autor(en) / Beteiligte
- Titel
- Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling pathway
- Ist Teil von
- Molecular medicine reports, 2018-05, Vol.17 (5), p.7372-7380
- Ort / Verlag
- Greece: Spandidos Publications
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Liraglutide, a modified form of glucagon‑like peptide‑1 (GLP‑1), is used in the treatment of diabetes mellitus. However, the underlying mechanism by which liraglutide improves liver insulin resistance remains to be elucidated. The proto‑oncogene Wnt (Wnt) signaling pathway has been reported to be associated with glucose and lipid metabolism. Using in vivo and in vitro models of diabetes and insulin resistance, it was investigated whether the beneficial effects of liraglutide on liver glucose metabolism are mediated by the Wnt signaling pathway. The results of the present study demonstrate that body weight, fasting blood glucose, insulin levels and the homeostasis model assessment for insulin resistance were markedly decreased in db/db mice treated with liraglutide compared with control mice. Liraglutide also improved liver morphology and reduced the accumulation of lipid droplets. Furthermore, the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was downregulated, whereas the expression of phosphorylated forkhead box O1, Wnt signaling pathway‑associated molecules, β‑catenin, transcription factor 7‑like 2 and phosphorylated glycogen synthase kinase-3β was upregulated in the liver of mice treated with liraglutide. In the in vitro study, increased gluconeogenesis and decreased glucose uptake rates were observed in insulin resistant hepatocytes; treatment with liraglutide significantly reversed this effect. Furthermore, transfection of insulin resistant hepatocytes with β‑catenin small interfering RNA attenuated the effects of liraglutide, suggesting that liraglutide improves insulin resistance via activating the β‑catenin/Wnt signaling pathway. The results of the present study suggest a novel mechanism underlying liraglutide‑mediated improvements in insulin resistance in the liver. The Wnt signaling pathway may be a potential therapeutic target for the treatment of altered hepatic physiology in insulin resistance.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1791-2997eISSN: 1791-3004DOI: 10.3892/mmr.2018.8737Titel-ID: cdi_proquest_miscellaneous_2018016412
- Format
- –
- Schlagworte
- Analysis, Animal models, Animals, Antidiabetics, Blood glucose, Blood Glucose - metabolism, Body weight, Complications and side effects, Development and progression, Diabetes mellitus, Diabetes Mellitus - drug therapy, Diabetes Mellitus - metabolism, Diabetes Mellitus - pathology, Dosage and administration, Drug therapy, Forkhead protein, Genetic aspects, Glucagon, Glucagon-like peptide 1, Gluconeogenesis, Gluconeogenesis - drug effects, Glucose, Glucose - metabolism, Glucose-6-phosphatase, Glycogen, Glycogen synthase kinase 3, Hep G2 Cells, Hepatocytes, Homeostasis, Humans, Hypoglycemic Agents - pharmacology, Hypoglycemic Agents - therapeutic use, Insulin, Insulin Resistance, Kinases, Lipid metabolism, Liraglutide, Liraglutide - pharmacology, Liraglutide - therapeutic use, Liver, Liver - drug effects, Liver - metabolism, Liver - pathology, Male, Mice, Mice, Inbred C57BL, Risk factors, Rodents, Signal transduction, siRNA, Studies, Therapeutic applications, Transfection, Wnt protein, Wnt Signaling Pathway - drug effects, β-Catenin