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Gene Review

Slc16a3  -  solute carrier family 16 (monocarboxylate...

Rattus norvegicus

Synonyms: MCT 3, MCT 4, MCT4, Mct3, Mct4, ...
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Disease relevance of Slc16a3

  • We conclude that obesity leads to changes in muscular MCT1 and MCT4 expression, which, when associated with LDH isozyme redistribution, may contribute to the hyperlactatemia noted in insulin resistance [1].
  • Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia [2].

High impact information on Slc16a3


Chemical compound and disease context of Slc16a3

  • The present experiments were undertaken to characterize 1) the hindlimb muscle mass lactate uptake and 2) the expression of monocarboxylate transporter isoforms MCT1 and MCT4, as well as lactate dehydrogenase (LDH) isozyme distribution, in various skeletal muscles of Zucker fa/fa rats taken as a model of insulin resistance-related obesity [1].

Biological context of Slc16a3


Anatomical context of Slc16a3

  • Skeletal muscle contains both MCT1 (the only isoform found in erythrocytes but also present in most other cells) and MCT4 [7].
  • Furthermore, we hypothesized that MCT1 would be detected at interfibrillar as well as at subsarcolemmal and sarcolemmal cell domains, whereas MCT2 and MCT4 abundances would be most prominent at the sarcolemma [8].
  • In additional studies, the 10-min contraction period increased the plasma membrane GLUT4 (P < 0.05) while again reducing MCT4 (-20%, P < 0.05) but not MCT1 (P > 0.05) [5].
  • Using immunostaining techniques, we show that MCT4 localizes with its accessory protein CD147 in the basolateral membrane of rat thyroid follicular cells [9].
  • MCT4 was found exclusively in astrocytes in several areas including the cortex, the hippocampus, and the cerebellum [10].

Associations of Slc16a3 with chemical compounds

  • From the perspective of lactate shuttle hypotheses we posited that MCT1 would be highly expressed in oxidative fibres, whereas MCT4 would be found in highly glycolytic fibres [8].
  • These studies have shown that 1) with STZ-induced diabetes, MCT1 and MCT4 are reduced in skeletal muscle and/or the heart and 2) exercise training alleviated these diabetes-induced reductions [11].
  • These results demonstrate that lovastatin acid was largely taken up by mesangial cells via MCT, and suggest that MCT4 might contribute to lovastatin acid uptake in the cells [12].
  • After the animals were perfusion-fixed in 4% paraformaldehyde, the extensor digitorum longus muscle (EDL) and the soleus muscle (SOL) were dissected out and MCT1 and MCT4 localization were immunohistochemically determined in serial sections [13].

Other interactions of Slc16a3


Analytical, diagnostic and therapeutic context of Slc16a3

  • MCT1 expression is increased in response to chronic stimulation and either endurance or explosive exercise training in rats and humans, whereas denervation decreases expression of both MCT1 and MCT4 [7].
  • Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study [15].
  • The MCT4 protein content did not change in the plantaris muscle despite a decrease in transcript levels, related to hypoxia and caloric restriction [6].
  • On the basis of Northern and Western blot analyses, MCT1 is expressed in both the neural retina and the RPE, whereas the expression of MCT3 is restricted to the RPE [16].


  1. Impaired sarcolemmal vesicle lactate uptake and skeletal muscle MCT1 and MCT4 expression in obese Zucker rats. Py, G., Lambert, K., Perez-Martin, A., Raynaud, E., Préfaut, C., Mercier, J. Am. J. Physiol. Endocrinol. Metab. (2001) [Pubmed]
  2. Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia. McClelland, G.B., Brooks, G.A. J. Appl. Physiol. (2002) [Pubmed]
  3. Expression and distribution of lactate/monocarboxylate transporter isoforms in pancreatic islets and the exocrine pancreas. Zhao, C., Wilson, M.C., Schuit, F., Halestrap, A.P., Rutter, G.A. Diabetes (2001) [Pubmed]
  4. Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3. Wilson, M.C., Jackson, V.N., Heddle, C., Price, N.T., Pilegaard, H., Juel, C., Bonen, A., Montgomery, I., Hutter, O.F., Halestrap, A.P. J. Biol. Chem. (1998) [Pubmed]
  5. Muscle contraction increases lactate transport while reducing sarcolemmal MCT4, but not MCT1. Tonouchi, M., Hatta, H., Bonen, A. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  6. Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle. Py, G., Eydoux, N., Lambert, K., Chapot, R., Koulmann, N., Sanchez, H., Bahi, L., Peinnequin, A., Mercier, J., Bigard, A.X. Metab. Clin. Exp. (2005) [Pubmed]
  7. Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter. Juel, C., Halestrap, A.P. J. Physiol. (Lond.) (1999) [Pubmed]
  8. Immunohistochemical analysis of MCT1, MCT2 and MCT4 expression in rat plantaris muscle. Hashimoto, T., Masuda, S., Taguchi, S., Brooks, G.A. J. Physiol. (Lond.) (2005) [Pubmed]
  9. MCT1 and its accessory protein CD147 are differentially regulated by TSH in rat thyroid cells. Fanelli, A., Grollman, E.F., Wang, D., Philp, N.J. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  10. Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain. Pellerin, L., Bergersen, L.H., Halestrap, A.P., Pierre, K. J. Neurosci. Res. (2005) [Pubmed]
  11. Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats. Enoki, T., Yoshida, Y., Hatta, H., Bonen, A. J. Appl. Physiol. (2003) [Pubmed]
  12. Monocarboxylate transporter mediates uptake of lovastatin acid in rat cultured mesangial cells. Nagasawa, K., Nagai, K., Sumitani, Y., Moriya, Y., Muraki, Y., Takara, K., Ohnishi, N., Yokoyama, T., Fujimoto, S. Journal of pharmaceutical sciences. (2002) [Pubmed]
  13. Fiber type-specific localization of monocarboxylate transporters MCT1 and MCT4 in rat skeletal muscle. Kobayashi, M. The Kurume medical journal. (2004) [Pubmed]
  14. Chronic hypoxia- and monocrotaline-induced elevation of hypoxia-inducible factor-1 alpha levels and pulmonary hypertension. Lai, Y.L., Law, T.C. J. Biomed. Sci. (2004) [Pubmed]
  15. Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats. Lai, Y.L., Olson, J.W., Gillespie, M.N. J. Appl. Physiol. (1991) [Pubmed]
  16. Monocarboxylate transporter MCT1 is located in the apical membrane and MCT3 in the basal membrane of rat RPE. Philp, N.J., Yoon, H., Grollman, E.F. Am. J. Physiol. (1998) [Pubmed]
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