Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway
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 endoth...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2021/2936667 |
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| author | Han Wu Cheng Xiao Yiting Zhao Hongchao Yin Miao Yu |
| author_facet | Han Wu Cheng Xiao Yiting Zhao Hongchao Yin Miao Yu |
| author_sort | Han Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-031fab7cfde44e71b88bc0a8c8fa3d34 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-031fab7cfde44e71b88bc0a8c8fa3d342025-08-20T03:54:14ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/29366672936667Liraglutide Improves Endothelial Function via the mTOR Signaling PathwayHan Wu0Cheng Xiao1Yiting Zhao2Hongchao Yin3Miao Yu4Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, ChinaDepartment of PET-CT Center, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, ChinaDepartment of Pathology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, ChinaDepartment of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, ChinaBackground. 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.http://dx.doi.org/10.1155/2021/2936667 |
| spellingShingle | Han Wu Cheng Xiao Yiting Zhao Hongchao Yin Miao Yu Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway Journal of Diabetes Research |
| title | Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway |
| title_full | Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway |
| title_fullStr | Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway |
| title_full_unstemmed | Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway |
| title_short | Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway |
| title_sort | liraglutide improves endothelial function via the mtor signaling pathway |
| url | http://dx.doi.org/10.1155/2021/2936667 |
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