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New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation

BACKGROUND: Glucose cotransporter (SGLT) 2 suppression provides potent renal protective effect during diabetic kidney disease (DKD). This work aimed to explore how empagliflozin (EMPA, the selective and strong inhibitor of SGLT2) affected renal lipid deposition among patients undergoing type 2 diabe...

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Autores principales: Sun, Hong, Chen, Juan, Hua, Yulin, Zhang, Yuyang, Liu, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396853/
https://www.ncbi.nlm.nih.gov/pubmed/35999610
http://dx.doi.org/10.1186/s13098-022-00886-x
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author Sun, Hong
Chen, Juan
Hua, Yulin
Zhang, Yuyang
Liu, Zheng
author_facet Sun, Hong
Chen, Juan
Hua, Yulin
Zhang, Yuyang
Liu, Zheng
author_sort Sun, Hong
collection PubMed
description BACKGROUND: Glucose cotransporter (SGLT) 2 suppression provides potent renal protective effect during diabetic kidney disease (DKD). This work aimed to explore how empagliflozin (EMPA, the selective and strong inhibitor of SGLT2) affected renal lipid deposition among patients undergoing type 2 diabetes mellitus (T2DM), a T2DM mouse model and human renal proximal tubular epithelial (HK-2) cells. METHODS: This work divided subjects as 3 groups: non-diabetic volunteers, patients treated with metformin and those treated with metformin plus EMPA. In an in vivo study, EMPA was adopted for treating db/db mice that were raised with the basal diet or the high-advanced glycation end products (AGEs) diet. In addition, AGEs and/or EMPA was utilized to treat HK-2 cells in vitro. RESULTS: Results showed that diabetic patients treated with metformin plus EMPA had lower AGEs levels and renal fat fraction (RFF) than those treated with metformin. Moreover, a significant and positive association was found between AGEs and RFF. Results from the basic study showed that EMPA decreased cholesterol level, tubular lipid droplets, and protein levels related to cholesterol metabolism in AGEs-mediated HK-2 cells, kidneys of db/db mice and those fed with the high-AGEs diet. Additionally, EMPA decreased AGEs levels in serum while inhibiting the expression of receptor of AGEs (RAGE) in vitro and in vivo. CONCLUSION: EMPA inhibited the AGEs-RAGE pathway, thereby alleviating diabetic renal tubular cholesterol accumulation.
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spelling pubmed-93968532022-08-24 New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation Sun, Hong Chen, Juan Hua, Yulin Zhang, Yuyang Liu, Zheng Diabetol Metab Syndr Research BACKGROUND: Glucose cotransporter (SGLT) 2 suppression provides potent renal protective effect during diabetic kidney disease (DKD). This work aimed to explore how empagliflozin (EMPA, the selective and strong inhibitor of SGLT2) affected renal lipid deposition among patients undergoing type 2 diabetes mellitus (T2DM), a T2DM mouse model and human renal proximal tubular epithelial (HK-2) cells. METHODS: This work divided subjects as 3 groups: non-diabetic volunteers, patients treated with metformin and those treated with metformin plus EMPA. In an in vivo study, EMPA was adopted for treating db/db mice that were raised with the basal diet or the high-advanced glycation end products (AGEs) diet. In addition, AGEs and/or EMPA was utilized to treat HK-2 cells in vitro. RESULTS: Results showed that diabetic patients treated with metformin plus EMPA had lower AGEs levels and renal fat fraction (RFF) than those treated with metformin. Moreover, a significant and positive association was found between AGEs and RFF. Results from the basic study showed that EMPA decreased cholesterol level, tubular lipid droplets, and protein levels related to cholesterol metabolism in AGEs-mediated HK-2 cells, kidneys of db/db mice and those fed with the high-AGEs diet. Additionally, EMPA decreased AGEs levels in serum while inhibiting the expression of receptor of AGEs (RAGE) in vitro and in vivo. CONCLUSION: EMPA inhibited the AGEs-RAGE pathway, thereby alleviating diabetic renal tubular cholesterol accumulation. BioMed Central 2022-08-23 /pmc/articles/PMC9396853/ /pubmed/35999610 http://dx.doi.org/10.1186/s13098-022-00886-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sun, Hong
Chen, Juan
Hua, Yulin
Zhang, Yuyang
Liu, Zheng
New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
title New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
title_full New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
title_fullStr New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
title_full_unstemmed New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
title_short New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
title_sort new insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396853/
https://www.ncbi.nlm.nih.gov/pubmed/35999610
http://dx.doi.org/10.1186/s13098-022-00886-x
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