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Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway
- Source :
- Journal of Diabetes Research, Vol 2021 (2021), Journal of Diabetes Research
- Publication Year :
- 2021
- Publisher :
- Hindawi Limited, 2021.
-
Abstract
- Background. Mammalian target of rapamycin (mTOR) is crucial for endothelial function. This study is aimed at assessing whether the glucagon-like peptide-1 (GLP-1) analogue liraglutide has a protective effect on endothelial function via the mTOR signaling pathway. Methods. Human umbilical vein endothelial cells (HUVECs) were administered liraglutide (100 nM) for 0, 10, 30, 60, 720, and 1440 minutes, respectively. Then, the expression and phosphorylation levels of mTOR, mTOR-Raptor complex (mTORC1), and mTOR-Rictor complex (mTORC2) were determined by Western blot and immunoprecipitation, while mTORC1 and mTORC2 expression was blocked by siRNA-Raptor and siRNA-Rictor, respectively. Akt phosphorylation was detected by Western blot. HUVECs were then incubated with liraglutide in the absence or presence of Akt inhibitor IV. Nitric oxide (NO) release was assessed by the nitrate reductase method. Phosphorylated endothelial nitric oxide synthase (eNOS), human telomerase reverse transcriptase (hTERT), and apoptosis-related effectors were assessed for protein levels by Western blot. Telomerase activity was evaluated by ELISA. Results. Sustained mTOR phosphorylation, mTORC2 formation, and mTORC2-dependent Akt phosphorylation were induced by liraglutide. In addition, eNOS phosphorylation, NO production, nuclear hTERT accumulation, and nuclear telomerase activity were enhanced by mTORC2-mediated Akt activation. Liraglutide also showed an antiapoptotic effect by upregulating antiapoptotic proteins and downregulating proapoptotic proteins in an mTORC2-Akt activation-dependent manner. Conclusion. Liraglutide significantly improves endothelial function, at least partially via the mTORC2/Akt signaling pathway.
- Subjects :
- Article Subject
Endocrinology, Diabetes and Metabolism
Mechanistic Target of Rapamycin Complex 2
mTORC1
Mechanistic Target of Rapamycin Complex 1
Pharmacology
Incretins
mTORC2
Diseases of the endocrine glands. Clinical endocrinology
Endocrinology
Western blot
Human Umbilical Vein Endothelial Cells
medicine
Humans
Hypoglycemic Agents
Telomerase reverse transcriptase
Phosphorylation
Protein kinase B
Cells, Cultured
PI3K/AKT/mTOR pathway
medicine.diagnostic_test
Chemistry
Akt/PKB signaling pathway
TOR Serine-Threonine Kinases
Liraglutide
RC648-665
Proto-Oncogene Proteins c-akt
Signal Transduction
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23146753 and 23146745
- Volume :
- 2021
- Database :
- OpenAIRE
- Journal :
- Journal of Diabetes Research
- Accession number :
- edsair.doi.dedup.....71b0a21f1e724eec08147de165836000