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Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease

Schumann, T. and König, J. and Henke, C. and Willmes, D.M. and Bornstein, S.R. and Jordan, J. and Fromm, M.F. and Birkenfeld, A.L. (2020) Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease. Pharmacological Reviews, 72 (1), pp. 343-379. American Society for Pharmacology and Experimental Therapeutics (ASPET). doi: 10.1124/pr.118.015735. ISSN 0031-6997.

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Official URL: https://doi.org/10.1124/pr.118.015735

Abstract

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.

Item URL in elib:https://elib.dlr.de/134760/
Document Type:Article
Title:Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Schumann, T.UNSPECIFIEDUNSPECIFIED
König, J.UNSPECIFIEDUNSPECIFIED
Henke, C.UNSPECIFIEDUNSPECIFIED
Willmes, D.M.UNSPECIFIEDUNSPECIFIED
Bornstein, S.R.UNSPECIFIEDUNSPECIFIED
Jordan, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany; Jens.Jordan (at) dlr.dehttps://orcid.org/0000-0003-4518-0706
Fromm, M.F.UNSPECIFIEDUNSPECIFIED
Birkenfeld, A.L.UNSPECIFIEDUNSPECIFIED
Date:January 2020
Journal or Publication Title:Pharmacological Reviews
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:72
DOI :10.1124/pr.118.015735
Page Range:pp. 343-379
Publisher:American Society for Pharmacology and Experimental Therapeutics (ASPET)
ISSN:0031-6997
Status:Published
Keywords:solute carrier; protein transport; Metabolic Disease; SLC; treatment
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Vorhaben Systemphysiologie (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine
Institute of Aerospace Medicine > Leitungsbereich ME
Deposited By: Schrage, Larissa
Deposited On:29 Apr 2020 11:22
Last Modified:30 Sep 2020 10:34

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