Chris I Cheeseman
Department: Department of Physiology
Degree: PhD, Sheffield
Office: 7-55 Medical Sciences Building
Tel: 780.492.2620
Fax: 780.492.8915
E-mail:
Position
Chair, Department of Physiology
Research Area
The physiology and structure function studies of facilitated hexose transporters
Research Synopsis
-
Rapid Control of Intestinal Hexose Transport
We are studying how enteric peptide hormones can regulate the activity of two specific transport proteins expressed in intestinal epithelial cells (enterocytes). The abundance in the apical membrane of enterocytes of both the sodium-dependent glucose transporter, SGLT-1 and the facilitated hexose transporter GLUT2, is increased in minutes by the enteric hormone, glucagon-like peptide 2 (GLP-2). The exit of hexoses from the enterocytes to the blood is also mediated by GLUT-2 and GLP-2 up-regulates the functional activity of this protein in the basolateral membrane. Currently, the mechanism is unknown. -
Structure Function Studies of GLUT proteins
Recently, we cloned human GLUT7 a high affinity glucose/ fructose transporter found in the apical membrane of the distal small intestine. Computer modelling and site directed mutagenesis of this protein has led to the identification of a motif apparently responsible for determining the substrate specificity of GLUT proteins. Studies are now being extended to other members of the GLUT family. -
Development of Specific GLUT substrates for Use with PET Imaging
We are developing hexose analogues as unique substrates for individual GLUT proteins, for use with Positron Emission Tomography to image pancreatic islets non-invasively. -
Laboratory Techniques
This laboratory employs a mixture of classical physiological techniques along with molecular biology to address the specific questions outlined above. These include isolated membrane vesicle preparations, vascular perfusion of the small intestine, and isolated enterocytes. Molecular techniques include Western and Northern blotting, PCR, in situ hybridization, and expression cloning.
Keywords
hexose transporters, GLUT proteins, PET imaging, structure/ function studies.
Selected Publications
CI Cheeseman, R Tsang. The effect of gastric inhibitory polypeptide and glucagon-like peptides on intestinal hexose transport. American Journal of Physiology 271: G477-G482, 1996.
CI Cheeseman. Upregulation of SGLT-1 transport activity in the rat jejunum induced by GLP-2 infusion in vivo. American Journal of Physiology 273: R1965-R1971, 1997.
CI Cheeseman, D O'Neill. Basolateral D-glucose transport activity along the crypt villus axis in rat jejunum and upregulation induced by GIP and GLP-2. Experimental Physiology 83: 605-616, 1998.
Anita Au, Alina Gupta, Paul Schembri, Chris I Cheeseman. Rapid Insertion of GLUT2 into the Rat Jejunal Brush-Border Membrane Promoted by Glucagon-Like Peptide 2. Biochem J 367, 254, 2002.
NT Lam, AT Cheung, CI Cheeseman, TJ Kieffer. Leptin reduces glucose transport and cellular ATP levels in INS-1 b-cells. J. Mol Endocrinology, 32(2):415-24, 2004.
Qiang Li, Andrei Manolescu, Mabel Ritzel, Sylvia Yao, Melissa Slugoski, James D. Young, Xing-Zhen Chen & Chris I. Cheeseman. Cloning and Functional Characterization of the Human GLUT7 Isoform (SLC2A7) from the Small Intestine. Am. J. Physiol. 287(1):G236-42, 2004.
Andrea Scheepers, Stefan Schmidt, Andrei Manolescu, Chris I Cheeseman, Andreas Bell, Hans-Georg Joost and Annette Schürmann. Characterisation of the human SLC2A11 (GLUT11) gene: alternative promoter usage, function, expression, and subcellular distribution of three isoforms, and lack of mouse ortholog. Mol. Mem. Biol. 22(4):339-51, 2005.
Andrei Manolescu, Alexis M Salas-Burgos, Jorge Fischbarg, Chris I Cheeseman. Identification of a hydrophobic residue as a key determinant of fructose transport by the facilitative hexose transporter SLC2A7 (GLUT7). JBC 280(52):42978-83, 2005.
C Keembiyehetty, R Augustin, MO Marayannopoulos, S Steer, A Manolescu, CI Cheeseman, KH Moley. Mouse glucose transporter 9 (mGLUT9) splice variants are expressed in adult liver and kidney and are upregulated in diabetes. Mol Endocrinol. 20(3):686-97, 2005.
