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Schumann, T. ; König, J.* ; Henke, C. ; Willmes, D.M. ; Bornstein, S.R.* ; Jordan, J.* ; Fromm, M.F.* ; Birkenfeld, A.L.

Solute carrier transporters as potential targets for the treatment of metabolic disease.

Pharmacol. Rev. 72, 343-379 (2020)
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Open Access Hybrid
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The solute carrier (SLC) superfamily comprises more than 400 transport proteins mediating the influx and efflux of substances such as ions, nucleotides, and sugars across biological membranes. Over 80 SLC transporters have been linked to human diseases, including obesity and type 2 diabetes (T2D). This observation highlights the importance of SLCs for human (patho)physiology. Yet, only a small number of SLC proteins are validated drug targets. The most recent drug class approved for the treatment of T2D targets sodium-glucose cotransporter 2, product of the SLC5A2 gene. There is great interest in identifying other SLC transporters as potential targets for the treatment of metabolic diseases. Finding better treatments will prove essential in future years, given the enormous personal and socioeconomic burden posed by more than 500 million patients with T2D by 2040 worldwide. In this review, we summarize the evidence for SLC transporters as target structures in metabolic disease. To this end, we identified SLC13A5/sodium-coupled citrate transporter, and recent proof-of-concept studies confirm its therapeutic potential in T2D and nonalcoholic fatty liver disease. Further SLC transporters were linked in multiple genome-wide association studies to T2D or related metabolic disorders. In addition to presenting better-characterized potential therapeutic targets, we discuss the likely unnoticed link between other SLC transporters and metabolic disease. Recognition of their potential may promote research on these proteins for future medical management of human metabolic diseases such as obesity, fatty liver disease, and T2D.Significance Statement-Given the fact that the prevalence of human metabolic diseases such as obesity and type 2 diabetes has dramatically risen, pharmacological intervention will be a key future approach to managing their burden and reducing mortality. In this review, we present the evidence for solute carrier (SLC) genes associated with human metabolic diseases and discuss the potential of SLC transporters as therapeutic target structures.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Brown Adipose-tissue; Uncoupling Protein-2 Gene; Genome-wide Association; Coupled Citrate Transporter; Type-2 Diabetes-mellitus; Pancreatic Beta-cells; Fatty Liver-disease; Adaptive Nonshivering Thermogenesis; Glucose-galactose Malabsorption; Hepatic Insulin-resistance
Sprache englisch
Veröffentlichungsjahr 2020
Prepublished im Jahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 0031-6997
e-ISSN 1521-0081
Zeitschrift Pharmacological reviews
Quellenangaben Band: 72, Heft: 1, Seiten: 343-379 Artikelnummer: , Supplement: ,
Verlag American Society for Pharmacology and Experimental Therapeutics (ASPET)
Verlagsort Bethesda, Md.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
G-502600-012
DOI 10.1124/pr.118.015735
WOS ID WOS:000508021800009
Scopus ID 85077334709
Erfassungsdatum 2020-01-22
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