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Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice

PURPOSE: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. MATERIAL AND METHODS: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapaglifl...

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Autores principales: Nguyen, Thiquynhnga, Wen, Song, Gong, Min, Yuan, Xinlu, Xu, Dongxiang, Wang, Chaoxun, Jin, Jianlan, Zhou, Ligang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425107/
https://www.ncbi.nlm.nih.gov/pubmed/32848437
http://dx.doi.org/10.2147/DMSO.S258593
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author Nguyen, Thiquynhnga
Wen, Song
Gong, Min
Yuan, Xinlu
Xu, Dongxiang
Wang, Chaoxun
Jin, Jianlan
Zhou, Ligang
author_facet Nguyen, Thiquynhnga
Wen, Song
Gong, Min
Yuan, Xinlu
Xu, Dongxiang
Wang, Chaoxun
Jin, Jianlan
Zhou, Ligang
author_sort Nguyen, Thiquynhnga
collection PubMed
description PURPOSE: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. MATERIAL AND METHODS: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence. RESULTS: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. CONCLUSION: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.
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spelling pubmed-74251072020-08-25 Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice Nguyen, Thiquynhnga Wen, Song Gong, Min Yuan, Xinlu Xu, Dongxiang Wang, Chaoxun Jin, Jianlan Zhou, Ligang Diabetes Metab Syndr Obes Original Research PURPOSE: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. MATERIAL AND METHODS: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence. RESULTS: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. CONCLUSION: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function. Dove 2020-08-05 /pmc/articles/PMC7425107/ /pubmed/32848437 http://dx.doi.org/10.2147/DMSO.S258593 Text en © 2020 Nguyen et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Nguyen, Thiquynhnga
Wen, Song
Gong, Min
Yuan, Xinlu
Xu, Dongxiang
Wang, Chaoxun
Jin, Jianlan
Zhou, Ligang
Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
title Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
title_full Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
title_fullStr Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
title_full_unstemmed Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
title_short Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
title_sort dapagliflozin activates neurons in the central nervous system and regulates cardiovascular activity by inhibiting sglt-2 in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425107/
https://www.ncbi.nlm.nih.gov/pubmed/32848437
http://dx.doi.org/10.2147/DMSO.S258593
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