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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/R1570    most recent 00430.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Castillo, J. Articles by Planas, J. V. PubMed PubMed Citation Articles by Castillo, J. Articles by Planas, J. V.

Articles

Evolutionary structural and functional conservation of an ortholog of the GLUT2 glucose transporter gene (SLC2A2) in zebrafish

¹Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain; and ²Laboratory Institut de Recerca i Tecnologia Agroalimentaries-Institute of Marine Sciences, Consejo Superior de Investigaciones Científicas, Barcelona, Spain

Submitted July 20, 2009 ; accepted in final form September 16, 2009

In mammals, GLUT2 plays an essential role in glucose homeostasis. From an evolutionary perspective, relatively little is known about the biology of GLUT2, or other GLUTs, in nonmammalian vertebrates. Here, we have conducted studies to functionally characterize GLUT2 in zebrafish. First, we cloned the zebrafish ortholog of GLUT2 (zfGLUT2) encoding a protein of 504 amino acids with high-sequence identity to other known vertebrate GLUT2 proteins. The zfGLUT2 gene consists of 11 exons and 10 introns, spanning 20 kb and mapping to a region of chromosome 2 that exhibits conserved synteny with human chromosome 3. When expressed in Xenopus oocytes, zfGLUT2 transported 2-deoxyglucose (2-DG) with similar affinity than mammalian GLUT2 (K_m of 11 mM). Transport of 2-DG was competed mostly by D-fructose and D-mannose and was inhibited by cytochalasin B. During early development, zfGLUT2 expression was detected already at 10 h postfertilization and remained elevated in 5-day larvae, when it was clearly localized to the liver and intestinal bulb. In the adult, zfGLUT2 expression was highest in testis, brain, skin, kidney, and intestine, followed by liver and muscle. In the intestine, zfGLUT2 transcripts were detected in absorptive enterocytes, and its mRNA levels were altered by fasting and refeeding, suggesting that its expression in the intestine may be regulated by the nutritional status. These results indicate that the structure and function of GLUT2 has been remarkably well conserved during vertebrate evolution and open the way for the use of zebrafish as a model species in which to study the biology and pathophysiology of GLUT2.

gene expression; glucose transport; affinity; intestine