Glucose Transporters in Fish

Facilitative glucose transporters (GLUTs) are proteins that allow the diffusion of glucose into and out of cells and are important for glucose homeostasis in all organisms. Over the last fifteen years, our group has investigated the function and regulation of glucose transporters in fish. Our group was the first to identify the insulin-regulated glucose transporter 4 (GLUT4) in non-mammalian vertebrates and also the first to characterize the function and regulation of GLUT4 in fish. GLUT4Studies from our group have shown that GLUT4 in fish has similar glucose transport capabilities as its mammalian counterpart, albeit transporting glucose with a lower affinity. Furthermore, fish GLUT4 is regulated by insulin at the mRNA and protein levels and translocates to the plasma membrane in skeletal muscle and adipose cells in response to insulin, like mammalian GLUT4. Despite the similarities between fish and mammalian GLUT4 in terms of their regulation by insulin and other stimuli (e.g. cytokines, exercise, etc.), fish GLUT4 differs from mammalian GLUT4 in its traffic characteristics. These functional differences between mammalian and fish GLUT4 may explain the low ability of many fish species to achieve normoglucemia in a short time after feeding or administration of a glucose load. In our group, we are currently investigating the basis for the differences in intracellular traffic between fish and mammalian GLUT4 in relation to differences in protein motifs in GLUT4 that have been shown to be important for its intracellular traffic. We are currently studying the traffic behavior of chimeric fish-mammalian GLUT4 proteins in stable 3T3-L1 cells with emphasis on possible differences in intracellular endocytic routes. These studies may contribute to determine the domains in GLUT4 responsible for its traffic under basal and insulin-stimulation conditions in mammals. In addition  to GLUT4, we are also investigating the function and regulation of GLUT2, a low-affinity, high-capacity glucose transporter that is responsible in mammals for the output of glucose by the liver, for the pancreatic secretion of insulin, etc. We are conducting this research on the zebrafish and we are evaluating the effects of GLUT2 abrogation by antisense morpholinos during early development.


Related publications

Marín-Juez, R., Rovira, M., Crespo, D., van der Vaart, M., Spaink H. P., Planas, J. V. GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish. Journal of Cerebral Blood Flow and Metabolism. 2015. 35: 74-85.

Marín-Juez, R., Capilla, E., Simoes, F., Camps, M. Planas, JV. Structural and functional evolution of glucose transporter 4 (GLUT4): A look at GLUT4 in fish. 2014. In: Glucose Homeostasis. Ed.: L. Szablewski, pp. 37-68. InTech.

Marín-Juez R, Díaz M, Morata J, Planas JVMechanisms regulating GLUT4 transcription in skeletal muscle cells are highly conserved across vertebrates. PLoS ONE. 2013; 8(11): e80628.

Magnoni LJ, Vraskou Y, Palstra AP, Planas JV. AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells. PLoS ONE. 2012; 7(2): e31219.

Vraskou Y, Roher N, Diaz M, Antonescu CN, Mackenzie SA, Planas JV. Direct involvement of tumor necrosis factor {alpha} in the regulation of glucose uptake in rainbow trout muscle cells. Am J Physiol Regul Integr Comp Physiol. 2011; 300: 716-723.

Capilla E, Díaz M, Hou JC, Planas JV, Pessin JE. High basal cell surface levels of fish GLUT4 are related to reduced sensitivity of insulin-induced translocation toward GGA and AS160 inhibition in adipocytes. Am J Physiol Endocrinol Metab. 2010;298(2):E329-36.

Díaz M, Vraskou Y, Gutiérrez J, Planas JV. Expression of rainbow trout glucose transporters GLUT1 and GLUT4 during in vitro muscle cell differentiation and regulation by insulin and IGF-I. Am J Physiol Regul Integr Comp Physiol. 2009 ;296(3):R794-800.

Castillo J, Crespo D, Capilla E, Díaz M, Chauvigné F, Cerdà J, Planas JV. Evolutionary structural and functional conservation of an ortholog of the GLUT2 glucose transporter gene (SLC2A2) in zebrafish. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):R1570-81.

Antonescu CN, Díaz M, Femia G, Planas JV, Klip A. Clathrin-dependent and independent endocytosis of glucose transporter 4 (GLUT4) in myoblasts: regulation by mitochondrial uncoupling. Traffic. 2008;9(7):1173-90.

Roher N, Samokhvalov V, Díaz M, MacKenzie S, Klip A, Planas JV. The proinflammatory cytokine tumor necrosis factor-alpha increases the amount of glucose transporter-4 at the surface of muscle cells independently of changes in interleukin-6.Endocrinology. 2008;149(4):1880-9.

Díaz M, Capilla E, Planas JV. Physiological regulation of glucose transporter (GLUT4) protein content in brown trout (Salmo trutta) skeletal muscle. J Exp Biol. 2007 Jul;210(Pt 13):2346-51.

Díaz M, Antonescu CN, Capilla E, Klip A, Planas JV. Fish glucose transporter (GLUT)-4 differs from rat GLUT4 in its traffic characteristics but can translocate to the cell surface in response to insulin in skeletal muscle cells. Endocrinology. 2007;148(11):5248-57.

Capilla E, Díaz M, Albalat A, Navarro I, Pessin JE, Keller K, Planas JV. Functional characterization of an insulin-responsive glucose transporter (GLUT4) from fish adipose tissue. Am J Physiol Endocrinol Metab. 2004;287(2):E348-57.

Capilla E, Díaz M, Gutiérrez J, Planas JVPhysiological regulation of the expression of a GLUT4 homolog in fish skeletal muscle. Am J Physiol Endocrinol Metab. 2002;283(1):E44-9.

Planas JV, Capilla E, Gutiérrez J. Molecular identification of a glucose transporter from fish muscle. FEBS Lett. 2000;481(3):266-70.