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

Thiquynhnga Nguyen,* Song Wen,* Min Gong,* Xinlu Yuan, Dongxiang Xu, Chaoxun Wang, Jianlan Jin, Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lig...

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Autores principales:	Nguyen T, Wen S, Gong M, Yuan X, Xu D, Wang C, Jin J, Zhou L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	sodium glucose co-transporter-2 dapagliflozin c-fos cardiovascular activity brain nuclei Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/4920ff5917674a22a57b4c7404bfad51
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spelling	oai:doaj.org-article:4920ff5917674a22a57b4c7404bfad512021-12-02T12:29:41ZDapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice1178-7007https://doaj.org/article/4920ff5917674a22a57b4c7404bfad512020-08-01T00:00:00Zhttps://www.dovepress.com/dapagliflozin-activates-neurons-in-the-central-nervous-system-and-regu-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Thiquynhnga Nguyen,* Song Wen,* Min Gong,* Xinlu Yuan, Dongxiang Xu, Chaoxun Wang, Jianlan Jin, Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of ChinaTel +86 13611927616Email zhouligang@yahoo.comPurpose: 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.Keywords: sodium glucose co-transporter-2, dapagliflozin, c-Fos, cardiovascular activity, brain nucleiNguyen TWen SGong MYuan XXu DWang CJin JZhou LDove Medical Pressarticlesodium glucose co-transporter-2dapagliflozinc-foscardiovascular activitybrain nucleiSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 2781-2799 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	sodium glucose co-transporter-2 dapagliflozin c-fos cardiovascular activity brain nuclei Specialties of internal medicine RC581-951
spellingShingle	sodium glucose co-transporter-2 dapagliflozin c-fos cardiovascular activity brain nuclei Specialties of internal medicine RC581-951 Nguyen T Wen S Gong M Yuan X Xu D Wang C Jin J Zhou L Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice
description	Thiquynhnga Nguyen,* Song Wen,* Min Gong,* Xinlu Yuan, Dongxiang Xu, Chaoxun Wang, Jianlan Jin, Ligang Zhou Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, People’s Republic of ChinaTel +86 13611927616Email zhouligang@yahoo.comPurpose: 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.Keywords: sodium glucose co-transporter-2, dapagliflozin, c-Fos, cardiovascular activity, brain nuclei
format	article
author	Nguyen T Wen S Gong M Yuan X Xu D Wang C Jin J Zhou L
author_facet	Nguyen T Wen S Gong M Yuan X Xu D Wang C Jin J Zhou L
author_sort	Nguyen T
title	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_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_sort	dapagliflozin activates neurons in the central nervous system and regulates cardiovascular activity by inhibiting sglt-2 in mice
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/4920ff5917674a22a57b4c7404bfad51
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Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice

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