Empagliflozin (BI 10773) is a potent, competitive, and selective inhibitor of the sodium glucose transporter 2 (SGLT-2) with an IC50 of 3.1nM for hSGLT-2[1]. Empagliflozin can lower blood glucose levels by blocking SGLT2 cotransport protein in the proximal renal gyral tubule, promoting urinary glucose excretion, and preventing glucose reabsorption[2]. Empagliflozin is widely used in the treatment of type 2 diabetes, heart failure, chronic kidney and cancer[3].
Empagliflozin treatment for 72h can reduce high glucose induced TLR4 expression, NF-κB binding, IL-6 secretion, AP-1 binding and CIV expression in HK2 cells[4]. Empaglifozin (50µM, 24h) restored heparinase III-mediated glycocalyx (GCX) disruption and the normal mechanotransduction responses in GCX-compromised Human abdominal aortic endothelial cells (HAAECs)[5].
Empagliflozin (30mg/kg) supplementation protects mice from diet-induced weight gain, hyperglycaemic, hyperinsulinaemic and insulin resistant[6]. Long-term treatment with Empagliflozin (3mg/kg; 5 weeks) improves glycaemic control and features of metabolic syndrome in Zucker diabetic fatty rats[7].
References:
[1]. Grempler R, Thomas L, Eckhardt M, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors. Diabetes Obes Metab. 2012 Jan;14(1):83-90. doi: 10.1111/j.1463-1326.2011.01517.x. Epub 2011 Nov 13. PMID: 21985634.
[2]. Mascolo A, Di Napoli R, Balzano N, et al. Safety profile of sodium glucose co-transporter 2 (SGLT2) inhibitors: A brief summary. Front Cardiovasc Med. 2022 Sep 21;9:1010693. doi: 10.3389/fcvm.2022.1010693. PMID: 36211584; PMCID: PMC9532622.
[3]. Wu W, Wang Y, Xie J, et al. Empagliflozin: a potential anticancer drug. Discov Oncol. 2023 Jul 12;14(1):127. doi: 10.1007/s12672-023-00719-x. PMID: 37436535; PMCID: PMC10338413. [4]. Panchapakesan U, Pegg K, Gross S, et al. Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy? PLoS One. 2013;8(2):e54442. doi: 10.1371/journal.pone.0054442. Epub 2013 Feb 4. PMID: 23390498; PMCID: PMC3563635.
[5]. Cooper S, Teoh H, Campeau MA, et al. Empagliflozin restores the integrity of the endothelial glycocalyx in vitro. Mol Cell Biochem. 2019 Sep;459(1-2):121-130. doi: 10.1007/s11010-019-03555-2. Epub 2019 May 24. PMID: 31127491.
[6]. Radlinger B, Ress C, Folie S, et al. Empagliflozin protects mice against diet-induced obesity, insulin resistance and hepatic steatosis. Diabetologia. 2023 Apr;66(4):754-767. doi: 10.1007/s00125-022-05851-x. Epub 2022 Dec 16. PMID: 36525084; PMCID: PMC9947060.
[7]. Thomas L, Grempler R, Eckhardt M, et al. Long-term treatment with empagliflozin, a novel, potent and selective SGLT-2 inhibitor, improves glycaemic control and features of metabolic syndrome in diabetic rats. Diabetes Obes Metab. 2012 Jan;14(1):94-6. doi: 10.1111/j.1463-1326.2011.01518.x. Epub 2011 Nov 13. PMID: 21985693.
Empagliflozin (BI 10773)是一种强效、竞争性、选择性的钠-葡萄糖共转运蛋白2（SGLT-2）抑制剂，对人源SGLT-2的IC50值为3.1nM[1]。Empagliflozin可以通过抑制肾脏近曲小管中的SGLT-2共转运蛋白，促进尿糖排泄，阻止葡萄糖重吸收，从而有效降低血糖水平[2]。Empagliflozin广泛应用于2型糖尿病、心力衰竭、慢性肾病及癌症的治疗研究[3]。
在HK2细胞中，Empagliflozin处理72小时可显著降低高糖诱导的TLR4表达、NF-κB结合、IL-6分泌、AP-1结合及CIV表达[4]。Empagliflozin（50µM，24小时）能够修复肝素酶III介导的糖萼（GCX）损伤，并恢复人腹主动脉内皮细胞（HAAECs）中糖萼受损后的正常机械传导反应[5]。
在小鼠模型中，Empagliflozin（30mg/kg）能够有效预防饮食诱导的体重增加、高血糖、高胰岛素血症及胰岛素抵抗[6]。长期使用Empagliflozin（3mg/kg，5周）可改善Zucker糖尿病肥胖大鼠的血糖控制及代谢综合征特征[7]。