This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, L. Articles by Powers, A. C. Search for Related Content PubMed PubMed Citation Articles by Wu, L. Articles by Powers, A. C.

Different Functional Domains of GLUT2 Glucose Transporter Are Required for Glucose Affinity and Substrate Specificity¹

Division of Endocrinology, Department of Medicine (L.W., A.C.P.), and the Department of Pharmacology (J.D.F.), Vanderbilt University; and the Department of Veterans Affairs Medical Center (A.C.P.), Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Dr. Alvin C. Powers, Division of Endocrinology, 715 MRB II, Vanderbilt University, Nashville, Tennessee 37232. E-mail: Al.Powers{at}mcmail.vanderbilt.edu

GLUT2 is the major glucose transporter in pancreatic ß-cells and hepatocytes. It plays an important role in insulin secretion from ß-cells and glucose metabolism in hepatocytes. To better understand the molecular determinants for GLUT2’s distinctive glucose affinity and its ability to transport fructose, we constructed a series of chimeric GLUT2/GLUT3 proteins and analyzed them in both Xenopus oocytes and mammalian cells. The results showed the following. 1) GLUT3/GLUT2 chimera containing a region from transmembrane segment 9 to part of the COOH-terminus of GLUT2 had K_m values for 3-O-methylglucose similar to those of wild-type GLUT2. Further narrowing of the GLUT2 component in the chimeric GLUTs lowered the K_m values to those of wild-type GLUT3. 2) GLUT3/GLUT2 chimera containing a region from transmembrane segment 7 to part of the COOH-terminus of GLUT2 retained the ability to transport fructose. Further narrowing of this region in the chimeric GLUTs resulted in a complete loss of the fructose transport ability. 3) Chimeric GLUTs with the NH₂-terminal portion of GLUT2 were unable to express glucose transporter proteins in either Xenopus oocytes or mammalian RIN 1046-38 cells. These results indicate that amino acid sequences in transmembrane segments 9–12 are primarily responsible for GLUT2’s distinctive glucose affinity, whereas amino acid sequences in transmembrane segments 7–8 enable GLUT2 to transport fructose. In addition, certain region(s) of the amino-terminus of GLUT2 impose strict structural requirements on the carboxy-terminus of the glucose transporter protein. Interactions between these regions and the carboxy-terminus of GLUT2 are essential for GLUT2 expression.

This article has been cited by other articles:

				J. R. Hall, C. E. Short, and W. R. Driedzic Sequence of Atlantic cod (Gadus morhua) GLUT4, GLUT2 and GPDH: developmental stage expression, tissue expression and relationship to starvation-induced changes in blood glucose J. Exp. Biol., November 15, 2006; 209(22): 4490 - 4502. [Abstract] [Full Text] [PDF]

				L. Wu, W. Nicholson, S. M. Knobel, R. J. Steffner, J. M. May, D. W. Piston, and A. C. Powers Oxidative Stress Is a Mediator of Glucose Toxicity in Insulin-secreting Pancreatic Islet Cell Lines J. Biol. Chem., March 26, 2004; 279(13): 12126 - 12134. [Abstract] [Full Text] [PDF]

				C. J. Woodrow, R. J. Burchmore, and S. Krishna Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes PNAS, August 29, 2000; 97(18): 9931 - 9936. [Abstract] [Full Text] [PDF]