2. Academic Validation
  3. Epoxyeicosatrienoic acids improve glucose homeostasis by preventing NF-κB-mediated transcription of SGLT2 in renal tubular epithelial cells

Epoxyeicosatrienoic acids improve glucose homeostasis by preventing NF-κB-mediated transcription of SGLT2 in renal tubular epithelial cells

  • Mol Cell Endocrinol. 2021 Mar 1;523:111149. doi: 10.1016/j.mce.2020.111149.
Menglu Fu 1,  Jing Yu 2,  Zhihui Chen 2,  Ying Tang 2,  Ruolan Dong 3,  Yan Yang 4,  Jinlan Luo 2,  Shuiqing Hu 5,  Ling Tu 6,  Xizhen Xu 7
Affiliations

Affiliations

  • 1 Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 3 Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 4 Division of Endocrinology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 5 Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China.
  • 6 Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address: lingtu@tjh.tjmu.edu.cn.
  • 7 Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China. Electronic address: xzxu@tjh.tjmu.edu.cn.
PMID: 33387601 DOI: 10.1016/j.mce.2020.111149
Abstract

Studies have shown that epoxyeicosatrienoic acids (EETs) can regulate glucose homeostasis, but the specific mechanisms need further exploration. The sodium-glucose co-transporter 2 (SGLT2) is highly expressed in diabetic kidneys, which further promotes renal reabsorption of glucose to respond to the hyperglycemic state of diabetes. Herein, whether EETs can be a latent inhibitor of SGLT2 to regulate glucose homeostasis in diabetic state needs to be elucidated. Our study demonstrated that EETs attenuated the glucose reabsorption via renal tubular epithelial cells in diabetic mice, which partly accounted for the beneficial effects of EETs on glucose homeostasis. Moreover, 14,15-EET suppressed SGLT2 expression in both diabetic kidney and renal tubular epithelial cells. Further, inhibition of NF-κB with BAY 11-7082 decreased insulin-induced SGLT2 expression while NF-κB overexpression reversed the above effects. In addition, 14,15-EET attenuated SGLT2 expression via inactivating NF-κB. Mechanistically, 14,15-EET attenuated NF-κB mediated SGLT2 transcription at the -1821/-1812 P65-binding site. These results showed that EETs ameliorated glucose homeostasis via preventing NF-κB-mediated transcription of SGLT2 in renal tubular epithelial cells, providing a unique therapeutic strategy for Insulin resistance and diabetes.

Keywords

Diabetes; Epoxyeicosatrienoic acids; NF-κB; SGLT2; Soluble epoxide hydrolase.

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