钠-葡萄糖共转运蛋白及其抑制剂在2型糖尿病合并心血管疾病中的研究进展

Journal: Journal of Rural Medicine DOI: 10.12238/jrm.v1i2.11490

俞雅萌, 张欣, 贾敏

西安医学院基础与转化医学研究所

Abstract

高血糖是诱发老年心血管疾病的独立风险因素之一。目前临床推荐糖尿病伴有心血管疾病应尽早使用钠-葡萄糖共转运蛋白2抑制剂(SGLT-2i),很多大型临床试验中心的研究结果表明SGLT-2i可以降低动脉粥样硬化、高血压、心力衰竭以及慢性肾病的死亡率,但其具体的作用机制和疗效尚不清楚。本文将通过对SGLTs及其抑制剂在2型糖尿病合并心血管疾病发生和发展中的研究进展作一综述。

Keywords

钠-葡萄糖共转运蛋白;SGLT-2;SGLT抑制剂;心血管疾病

Funding

陕西省科技厅项目2023-JC-YB-753;陕西省教育厅重点实验室22JS038;西安医学院校级科技创新团队2021TD06。

References

[1] Association AD.10.Cardiovascular disease and risk man agement: Standards of medical care in diabetes-2019[J].Diab etes Care.2019,42(Suppl 1):S103-S123.
[2] American Diabetes Association.Standards of Medical Care in Diabetes-2022.Diabetes Care.2022,45(Suppl1):S1-S258.
[3] Zhao FQ,Keating AF.Functional properties and genomicsof glucose transporters[J].Curr Genomics.2007,8(2):113-128.
[4] Soták M,Casselbrant A,Rath E,et al.Intestinal sodium/ glucose cotransporter 3 expression is epithelial and downre gulated in obesity[J].Life Sci,2021,267:118974.
[5] Kothinti RK, Blodgett AB, North PE, et al. A novel SGLT is expressed in the human kidney[J].Eur J Pharmacol. 2012, 690(1-3):77-83.
[6] Tazawa S,Yamato T,Fujikura H,et al. SLC5A9/SGLT4, a new Na+-dependent glucose transporter,is an essential transpor ter for mannose,1,5-anhydro-D-glucitol,and fructose[J].Life Sci.2005,76(9):1039-1050.
[7] Grempler R, Augustin R, Froehner S, et al. Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter[J].FEBS Lett.2012,586 (3):248-253.
[8] Lin X, Ma L, Fitzgerald RL, et al.Human Sodium/Inositol Cotransporter 2 (SMIT2) Transports Inositols But Not Glucose in L6 Cells[J].Arch Biochem Biophys. 2009, 481(2):197-201.
[9] Kasichayanula S,Liu X,Lacreta F,etal.Clinical Pharmaco kinetics and Pharmacodynamics of Dapagliflozin, a Selective Inhibitor of Sodium-Glucose Co-transporter Type 2[J]. Clin Pharmacokinet.2014,53(1):17-27.
[10] El-Sayed N,Mostafa YM,AboGresha NM,et al.Dapaglifloz in attenuates diabetic cardiomyopathy through erythropoie tin up-regulation of AKT/JAK/MAPK pathways in streptozotocin -induced diabetic rats[J].Chem Biol Interact.2021,347:109617.
[11] Uthman L, Baartscheer A, Bleijlevens B, et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ exchanger, lowering of cytosolic Na+ and vasodilation[J].Diabetologia.2018,61(3):722-726.
[12] Sato T,Aizawa Y,Yuasa S,et al.The effect of dapaglifl ozin treatment on epicardial adipose tissue volume[J]. Cardi ovasc Diabetol.2018,Jan4;17(1):6.
[13] Zelniker TA, Bonaca MP, Furtado RHM, et al. Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial[J]. Circulation.2020,141(15):1227-1234.
[14] Devineni D,Polidori D.Clinical Pharmacokinetic, Phar macodynamic, and Drug–Drug Interaction Profile of Canaglif lozin, a Sodium-Glucose Co-transporter 2 Inhibitor[J]. Clin Pharmacokinet.2015, 54(10):1027-1041.
[15] Weir MR, McCullough PA, Buse JB, et al. Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results[J].Am J Nephrol.2020,51(4):276-288.
[16] Kondo H, Akoumianakis I, Badi I, et al. Effects of canagliflozin on human myocardial redox signalling: clinical implications[J].Eur Heart J.2021,42(48):4947-4960.
[17] Sayour AA, Korkmaz-Icöz S, Loganathan S, et al. Acute canagliflozin treatment protects against in vivo myocardial ischemia-reperfusion injury in non-diabetic male rats and enhances endothelium-dependent vasorelaxation[J]. J Transl Med.2019,17(1):127.
[18] Ashry NA,Abdelaziz RR,Suddek GM,et al.Canagliflozin ameliorates aortic and hepatic dysfunction in dietary-induc ed hypercholesterolemia in the rabbit[J]. Life Sci. 2021, 280:119731.
[19] Behnammanesh G,Durante GL,Khanna YP,et al.Canagliflo zin inhibits vascular smooth muscle cell proliferation and migration: Role of heme oxygenase-1[J]. Redox Biol. 2020, 32: 101527.
[20] Tahara A, Kurosaki E, Yokono M, et al. Pharmacological profile of ipragliflozin (ASP1941), a novel selective SGLT2 inhibitor, in vitro and in vivo[J]. Naunyn Schmiedebergs Arch Pharmacol.2012,385(4):423-436.
[21] Ito H, Okamoto R, Ali Y, et al. Cardiorenal protective effects of sodium-glucose cotransporter 2 inhibition in com bination with angiotensin II type 1 receptor blockade in salt -sensitive Dahl rats[J].J Hypertens.2022,40(5):956-968.
[22] Kang SM, Yun HM, Sohn M, et al. Vascular and metabolic effects of ipragliflozin versus sitagliptin (IVS) in type 2 diabetes treated with sulphonylurea and metformin: IVS study[J].Diabetes Obes Metab.2023,18.
[23] Akasaka H, Sugimoto K, Shintani A, et al. Effects of ipragliflozin on left ventricular diastolic function in patie nts with type 2 diabetes and heart failure with preserved ejection fraction: The EXCEED randomized controlled multice nter study[J].Geriatr Gerontol Int.2022,22(4):298-304.
[24] 谢少斐,张凤逸,邹珊,等.已上市钠-葡萄糖协同转运蛋白2抑制剂临床药动学特点比较[J].中国现代应用药学,2016,33(04):517-520.
[25] Bouchi R,Terashima M,Sasahara Y,et al.Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes:a pilot study[J].Cardiovasc Diabetol.2017,16(1):32.
[26] Mori Y,Terasaki M,Hiromura M,et al.Luseogliflozin attenuates neointimal hyperplasia after wire injury in highfat diet-fed mice via inhibition of perivascular adipose tissue remodeling[J].Cardiovasc Diabetol.2019,18(1):143.
[27] Nakashima M,Miyoshi T,Ejiri K,et al.Effects of luseog liflozin on estimated plasma volume in patients with heartfailure with preserved ejection fraction[J]. ESC Heart Fail. 2022,9(1):712-720.
[28] Seino Y. Luseogliflozin for the treatment of type 2 diabetes[J].Expert Opin Pharmacother.2014,15(18):2741-2749.
[29] Scheen AJ.Pharmacokinetic and pharmacodynamic prof ile of empagliflozin, a sodium glucose co-transporter 2 inhib itor[J].Clin Pharmacokinet.2014,53(3):213-225.
[30] Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension[J].Diabetes Care.2015,38(3):420-428.
[31] Shao Q, Meng L, Lee S, et al. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remod eling and improves mitochondrial function in high-fat diet /streptozotocin-induced diabetic rats[J].Cardiovasc Diabetol. 2019,18(1):165.
[32] Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, et al. Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics[J].2019,73(15):1931-1944.
[33] Andreadou I,Efentakis P,Balafas E,et al. Empagliflozin Limits Myocardial Infarction in Vivo and Cell Death in Vitro: Role of STAT3, Mitochondria, and Redox Aspects[J]. Front Physiol.2017,8:1077.
[34] Yurista SR, Silljé HHW, Oberdorf-Maass SU, et al. Sodium-glucose co-transporter 2 inhibition with empaglifloz in improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction[J]. Eur J Heart Fail.2019,21(7):862-873.
[35] Herat LY, Matthews VB, Magno AL, et al. An evaluation of empagliflozin and it's applicability to hypertension as a therapeutic option[J].Expert Opin Pharmacother.2020,21(10): 1157-1166.
[36] von Lewinski D,Kolesnik E,Tripolt NJ,et al.Empaglifloz in in acute myocardial infarction: the EMMY trial[J]. Eur Heart J.2022,43(41):4421-4432.
[37] Cosentino F, Cannon CP, Cherney DZI, et al. Efficacy of Ertugliflozin on Heart Failure-Related Events in Patients With Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease: Results of the VERTIS CV Trial[J]. Circulation. 2020,142(23):2205-2215.
[38] Moellmann J,Mann PA,Kappel BA,et al.The sodium-gluco se co-transporter-2 inhibitor ertugliflozin modifies the signature of cardiac substrate metabolism and reduces card iac mTOR signalling, endoplasmic reticulum stress and apopto sis[J].Diabetes Obes Metab.2022,24(11):2263-2272.
[39] Markham A,Keam SJ.Sotagliflozin:First Global Approval [J]Drugs.2019,79(9):1023-1029.
[40] Koufakis T, Mustafa OG, Tsimihodimos V, et al. Insights Into the Results of Sotagliflozin Cardiovascular Outcome Trials:Is Dual Inhibition the Cherry on the Cake of CardiorenalProtection?[J].Drugs.2021,81(12):1365-1371.
[41] Vallianou NG, Christodoulatos GS, Kounatidis D,et al. Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor: In the heart of the problem[J].Metabol Open.2021,10:100089.
[42] Bode D, Semmler L, Wakula P , et al. Dual SGLT-1 and SGLT-2 inhibition improves left atrial dysfunction in HFpEF [J].Cardiovasc Diabetol.2021,20(1):7.
[43] Posch MG, Walther N, Ferrannini E, et al. Metabolic, Intestinal,and Cardiovascular Effects of Sotagliflozin Comp ared With Empagliflozin in Patients With Type 2 Diabetes: A Randomized, Double-Blind Study[J].Diabetes Care.2022,45(9): 2118-2126.

Copyright © 2024 俞雅萌, 张欣, 贾敏

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License