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

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

  • Diabetol Metab Syndr. 2022 Aug 23;14(1):121. doi: 10.1186/s13098-022-00886-x.
Hong Sun  # 1 Juan Chen  # 2 Yulin Hua 3 Yuyang Zhang 4 Zheng Liu 5
Affiliations

Affiliations

  • 1 Department of Endocrinology and Metabolism, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou, Jiangsu, China. sunhong_611@126.com.
  • 2 Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
  • 3 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • 4 The First Clinical Medical College, Soochow University, Suzhou, Jiangsu, China.
  • 5 Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. liuzheng06@suda.edu.cn.
  • # Contributed equally.
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.

Keywords

Advanced glycation end products; Diabetic kidney disease; Empagliflozin; Renal fat fractions.

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