TABLE 1

Potential SLC targets for the treatment of metabolic disease with strong evidence based on human studies and mouse models

SLC NameProtein NameSubstratesExpression in Metabolically Active OrgansSubcellular LocalizationLink to Metabolic Disease in HumansLink to Metabolic Disease in MiceReferences
SLC5A1SGLT1Glucose, galactoseKidney, intestinePlasma membraneGlucose/galactose malabsorptionGlucose/galactose malabsorption, impaired glucose toleranceTurk et al., 1991; Martin et al., 1996; Kasahara et al., 2001; Wright et al., 2011; Powell et al., 2013; Wright, 2013
SLC5A2SGLT2GlucoseKidneyPlasma membraneFamilial glucosuriaObesity, insulin resistance, diabetesSanter et al., 2000, 2003; van den Heuvel et al., 2002; Jurczak et al., 2011; Wright et al., 2011; Powell et al., 2013; Wright, 2013
SLC13A5NaCT, NaC2, INDYCitrate, succinate, malate, fumarateLiver, brain, adrenal glandsPlasma membraneObesity, NAFLDObesity, fatty liver, insulin resistanceBirkenfeld et al., 2011; Bergeron et al., 2013; Pesta et al., 2015; Brachs et al., 2016; von Loeffelholz et al., 2017b
SLC16A1MCT1Lactate, pyruvate, ketone bodiesIntestine, heart, skeletal muscle, liver, kidney, adrenal glands, brain, adipose tissuePlasma membraneKetoacidosis, exercise- induced hyperinsulinemiaExercise-induced hyperinsulinemia, obesity, insulin resistance, hepatic steatosisHalestrap and Meredith, 2004; Otonkoski et al., 2007; Pullen et al., 2012; Lengacher et al., 2013; van Hasselt et al., 2014; Balasubramaniam et al., 2016; Carneiro et al., 2017
SLC16A11MCT11PyruvateThyroid, liverEndoplasmic reticulum, plasma membraneT2DFatty liver, insulin resistance, diabetesWilliams et al., 2014; Lara-Riegos et al., 2015; Traurig et al., 2016; Rusu et al., 2017; Almeda-Valdes et al., 2019; Hidalgo et al., 2019; Zhao et al., 2019b
SLC16A13MCT13UnknownLiver, kidney, intestineGolgi apparatusT2DN.A.Hara et al., 2014; Williams et al., 2014
SLC25A7UCP1, thermogeninH+Brown adipose tissueInner mitochondrial membraneObesity, T2DObesityNicholls et al., 1978; Lowell et al., 1993; Kopecky et al., 1995; Kopeck√Ĺ et al., 1996a,b; Baumruk et al., 1999; Li et al., 2000; Palmieri, 2004; Gates et al., 2007; Brondani et al., 2012
SLC25A8UCP2, UCPHH+Adipose tissue, skeletal muscle, liver, kidney, pancreas, heartInner mitochondrial membraneObesity, T2DObesityFleury et al., 1997; Gimeno et al., 1997; Arsenijevic et al., 2000; Zhang et al., 2001; Palmieri, 2013; Dalgaard, 2011
SLC25A9UCP3H+Skeletal muscleInner mitochondrial membraneObesity, T2DObesityBoss et al., 1997; Lowell, 1999; Clapham et al., 2000; Gong et al., 2000; Vidal-Puig et al., 2000; Horvath et al., 2003; Jia et al., 2009; Palmieri, 2013
SLC25A13AGC2, CTLN2, citrin aralar 2Aspartate, glutamateLiver, kidney, intestine, brain, pancreas, heart, skeletal muscle, adrenal glandsInner mitochondrial membraneNICCD, CTLN2CitrullinemiaKobayashi et al., 1999; Ohura et al., 2001; Tazawa et al., 2001; Sinasac et al., 2004; Saheki and Song, 2005; Takagi et al., 2006; Tsai et al., 2006; Saheki et al., 2007; Fukumoto et al., 2008; Komatsu et al., 2008; Chang et al., 2011; Palmieri, 2013; Hayasaka et al., 2018
SLC25A20CAC, CACTCarnitine, acylcarnitineLiver, intestine, adrenal glands, heart, skeletal muscle, kidney, brain, pancreasInner mitochondrial membraneCarnitine carrier deficiencyN.A.Huizing et al., 1997; Indiveri et al., 2011; Palmieri, 2013
SLC25A24APC1, MCSC1, SCAMC1Adenine nucleotides, phosphateIntestine, adipose tissue, adrenal glands, liver, pancreas, kidneyInner mitochondrial membraneObesityObesityPalmieri, 2013; Urano et al., 2015; Palmieri and Monne, 2016
SLC30A8ZnT8ZincPancreasSecretory granuleT2DObesity, insulin resistanceChimienti et al., 2004; Saxena et al., 2007; Scott et al., 2007; Sladek et al., 2007; Boesgaard et al., 2008; Nicolson et al., 2009; Pound et al., 2009, 2012; Tamaki et al., 2009, 2013; Cauchi et al., 2010; Wijesekara et al., 2010; Kim et al., 2011; Flannick et al., 2014; Gerber et al., 2014; Shan et al., 2014; Maruthur et al., 2015; Rutter and Chimienti, 2015; Mitchell et al., 2016; Li et al., 2017a, 2018; Wong et al., 2017; Ding et al., 2018; Dong et al., 2018; Kleiner et al., 2018; Lin et al., 2018; Liu et al., 2018; Plengvidhya et al., 2018