New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Diabetology & Metabolic Syndrome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13098-022-00886-x |
| _version_ | 1811281151861456896 |
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| author | Hong Sun Juan Chen Yulin Hua Yuyang Zhang Zheng Liu |
| author_facet | Hong Sun Juan Chen Yulin Hua Yuyang Zhang Zheng Liu |
| author_sort | Hong Sun |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T01:27:23Z |
| format | Article |
| id | doaj.art-3fde9d739bce402588ccf489899311ff |
| institution | Directory Open Access Journal |
| issn | 1758-5996 |
| language | English |
| last_indexed | 2024-04-13T01:27:23Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj.art-3fde9d739bce402588ccf489899311ff2022-12-22T03:08:35ZengBMCDiabetology & Metabolic Syndrome1758-59962022-08-0114111210.1186/s13098-022-00886-xNew insights into the role of empagliflozin on diabetic renal tubular lipid accumulationHong Sun0Juan Chen1Yulin Hua2Yuyang Zhang3Zheng Liu4Department of Endocrinology and Metabolism, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow UniversityDepartment of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese MedicineDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow UniversityThe First Clinical Medical College, Soochow UniversityDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow UniversityAbstract 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.https://doi.org/10.1186/s13098-022-00886-xDiabetic kidney diseaseAdvanced glycation end productsEmpagliflozinRenal fat fractions |
| spellingShingle | Hong Sun Juan Chen Yulin Hua Yuyang Zhang Zheng Liu New insights into the role of empagliflozin on diabetic renal tubular lipid accumulation Diabetology & Metabolic Syndrome Diabetic kidney disease Advanced glycation end products Empagliflozin Renal fat fractions |
| 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 | Diabetic kidney disease Advanced glycation end products Empagliflozin Renal fat fractions |
| url | https://doi.org/10.1186/s13098-022-00886-x |
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