Universität zu Köln

Schumann, Tina, Koenig, Joerg, Henke, Christine, Willmes, Diana M., Bornstein, Stefan R., Jordan, Jens, Fromm, Martin F. and Birkenfeld, Andreas L. ORCID: 0000-0003-1407-9023 (2020). Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease. Pharmacol. Rev., 72 (1). S. 343 - 380. BETHESDA: AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS. ISSN 1521-0081

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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 Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schumann, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenig, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Henke, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Willmes, Diana M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bornstein, Stefan R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jordan, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Fromm, Martin F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Birkenfeld, Andreas L. UNSPECIFIED orcid.org/0000-0003-1407-9023 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-352115
DOI:	10.1124/pr.118.015735
Journal or Publication Title:	Pharmacol. Rev.
Volume:	72
Number:	1
Page Range:	S. 343 - 380
Date:	2020
Publisher:	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Place of Publication:	BETHESDA
ISSN:	1521-0081
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 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 Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/35211