Recently it was determined that one of the facilitative glucose transporters, GLUT5, is an apically located protein in polarized epithelial cells which mediates the transport of fructose with high affinity. In contrast to the other members of the facilitative glucose transporter family, GLUT5 mediated fructose transport is much more efficient than glucose transport and fructose uptake is not inhibited by cytochalasin B. In the present application it is planned to exploit these unique properties of GLUT5 to determine functional domains of the facilitative glucose transporters. Specifically, chimeric glucose transporters will bc created between GLUT5 and the high affinity glucose transporter GLUT3 in order to localize the sequences which give rise to substrate specificities of GLUTS and GLUT3. These same chimeras will be used to determine the mechanism of cytochalasin B inhibition of glucose uptake. In separate experiments GLUT2 and GLUT5 will be transfected into the polarizable intestinal cell line, CaCo, and the route by which these transporters are targeted to either the basolateral or apical membranes respectively will bc determined. Subsequently, chimeric GLUT2/GLUT5 transporters will be expressed in CaCo cells to localize the sequences involved in directing the individual transporter to their unique subcellular site. These studies will increase the knowledge of the structure-function relationship among the glucose transporters. In addition, these experiments will help better understand the ways in which glucose and fructose enter cells and perhaps lead to ways in which the entry of glucose and other sugars into cell and out of the blood stream can be enhanced.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002170-03
Application #
2133946
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1993-07-01
Project End
1998-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Corpe, Christopher P; Bovelander, Floris J; Munoz, Christina M et al. (2002) Cloning and functional characterization of the mouse fructose transporter, GLUT5. Biochim Biophys Acta 1576:191-7
Chutkow, W A; Samuel, V; Hansen, P A et al. (2001) Disruption of Sur2-containing K(ATP) channels enhances insulin-stimulated glucose uptake in skeletal muscle. Proc Natl Acad Sci U S A 98:11760-4
Corpe, C; Sreenan, S; Burant, C (2001) Effects of type-2 diabetes and troglitazone on the expression patterns of small intestinal sugar transporters and PPAR-gamma in the Zucker diabetic fatty rat. Digestion 63:116-23
Chutkow, W A; Makielski, J C; Nelson, D J et al. (1999) Alternative splicing of sur2 Exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel. J Biol Chem 274:13656-65
Corpe, C P; Burant, C F; Hoekstra, J H (1999) Intestinal fructose absorption: clinical and molecular aspects. J Pediatr Gastroenterol Nutr 28:364-74
Sreenan, S; Keck, S; Fuller, T et al. (1999) Effects of troglitazone on substrate storage and utilization in insulin-resistant rats. Am J Physiol 276:E1119-29
Corpe, C P; Bovelander, F J; Hoekstra, J H et al. (1998) The small intestinal fructose transporters: site of dietary perception and evidence for diurnal and fructose sensitive control elements. Biochim Biophys Acta 1402:229-38
Burant, C F; Sreenan, S; Hirano, K et al. (1997) Troglitazone action is independent of adipose tissue. J Clin Invest 100:2900-8
Chutkow, W A; Simon, M C; Le Beau, M M et al. (1996) Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular KATP channels. Diabetes 45:1439-45
Corpe, C P; Burant, C F (1996) Hexose transporter expression in rat small intestine: effect of diet on diurnal variations. Am J Physiol 271:G211-6

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