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Schumann, T. ; König, J.* ; von Loeffelholz, C.* ; Vatner, D.F.* ; Zhang, D.* ; Perry, R.J.* ; Bernier, M.* ; Chami, J.* ; Henke, C. ; Kurzbach, A. ; El-Agroudy, N.N. ; Willmes, D.M. ; Pesta, D.* ; de Cabo, R.* ; O Sullivan, J.F.* ; Simon, E.* ; Shulman, G.I.* ; Hamilton, B.S.* ; Birkenfeld, A.L.

Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance.

Comm. Biol. 4:826 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Genome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Fatty Liver-disease; Induced Hepatic Steatosis; Monocarboxylate Transporter-1; Type-2; Variants; Lactate; Obesity; Association; Activation; Family
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Zeitschrift Communications Biology
Quellenangaben Band: 4, Heft: 1, Seiten: , Artikelnummer: 826 Supplement: ,
Verlag Springer
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute for Pancreatic Beta Cell Research (IPI)
Helmholtz AI - DLR (HAI - DLR)
Förderungen Intramural Research Program of the National Institute on Aging, NIH
Boehringer Ingelheim Pharma GmbH Co. KG
Deutsche Diabetes Gesellschaft (German Diabetes Association)
Deutsche Diabetes Gesellschaft (DDG)
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)