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

被引:5
|
作者
Le, Jiamei [1 ,2 ]
Chen, Yilong [2 ]
Yang, Wei [3 ]
Chen, Ligong [4 ]
Ye, Jianping [3 ,5 ]
机构
[1] Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Shanghai Key Lab Mol Imaging, Shanghai 201318, Peoples R China
[2] Univ Shanghai Sci & Technol, Sch Hlth Sci & Engn, Shanghai 200093, Peoples R China
[3] Zhengzhou Univ, Zhengzhou Cent Hosp, Metab Dis Res Ctr, Zhengzhou 450007, Peoples R China
[4] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China
[5] Zhengzhou Univ, Acad Med Sci, Res Ctr Basic Med, Zhengzhou 450052, Peoples R China
基金
中国国家自然科学基金;
关键词
Solute carriers (SLCs); Energy metabolism; ATP production; Type 2 diabetes mellitus (T2DM); Glucose homeostasis; Polymorphisms; ORGANIC CATION TRANSPORTER-2; OF-FUNCTION MUTATIONS; HIGH-FAT DIET; GENETIC-VARIATION; INSULIN-RESISTANCE; FUNCTIONAL-CHARACTERIZATION; SLCO1B1; POLYMORPHISM; THERAPEUTIC TARGETS; TRANSGENIC MICE; KIDNEY-DISEASE;
D O I
10.1016/j.apsb.2023.09.004
中图分类号
R9 [药学];
学科分类号
1007 ;
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 transporters 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 consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.
引用
收藏
页码:437 / 454
页数:18
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