Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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外文摘要：Solute carriers(SLCs)constitute the largest superfamily of membrane transporter proteins.These transporters,present in various SLC families,play a vital role in energy metabolism by facilitating the transport of diverse substances,including glucose,fatty acids,amino acids,nucleotides,and ions.They actively participate in the regulation of glucose metabolism at various steps,such as glucose uptake(e.g.,SLC2A4/GLUT4),glucose reabsorption(e.g.,SLC5A2/SGLT2),thermogenesis(e.g.,SLC25A7/UCP-1),and ATP production(e.g.,SLC25A4/ANT1 and SLC25A5/ANT2).The activities of these trans-porters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM).Notably,SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption,leading to groundbreaking advancements in diabetes drug discovery.Alongside SLC5A2,multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy.SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms,such as rosiglitazone(SLCO1B1/OATP1B1)and metformin(SLC22A1-3/OCT1-3 and SLC47A1,2/MATE1,2).By consoli-dating insights into the biological activities and clinical relevance of SLC transporters in T2DM,this re-view offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

外文关键词：

Solute carriers(SLCs)Energy metabolismATP productionType 2 diabetes mellitus(T2DM)Glucose homeostasisPolymorphisms

作者：

Jiamei Le、Yilong Chen、Wei Yang、Ligong Chen、Jianping Ye

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作者单位：

Shanghai Key Laboratory of Molecular Imaging,Zhoupu Hospital,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China

School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,China

Metabolic Disease Research Center,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China

School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China

Research Center for Basic Medicine,Academy of Medical Sciences,Zhengzhou University,Zhengzhou 450052,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaShanghai Key Laboratory of Molecular Imaging,ChinaClimbing Program of Shanghai University of Medicine and Health Sciences,China

项目编号：

81903961322712202020YFA09090008212780718DZ2260400A1-2601-23-311007

出版年：

2024

DOI：

10.1016/j.apsb.2023.09.004

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(2)

参考文献量191