The long-term objective is to understand solute transport across the intestinal epithelium. Particular emphasis will be placed on Na and glucose absorption during this phase of the project. The starting point is the recent cloning and functional expression of the brush border Na/glucose cotransporter in Xenopus oocytes.
The specific aims are as follows: 1) to describe the kinetics of Na/glucose cotransport. This will be accomplished by expression the transporter in Xenopus oocytes or COS 7 cells, and measuring 22Na and 14C-sugar fluxes, and sugar- dependent in ward Na currents. Fluxes and currents will be measured as a function of membrane voltage and extra- and intracellular substrate concentrations. 2) determine whether homology exists between the intestinal Na/glucose cotransporter and other cotransporters in the intestine and kidney. This will be accomplished by Northern and Western blots and the screening of cDNA libraries. 3) describe the expression of the Na/glucose contransporter as the immature enterocyte migrates from crypt to villus tip. Expression will be followed by in situ hybridization and immunocytochemical techniques, and processing of the protein from the endoplasmic reticulum to brush border membrane will be charted by Western blots of subcellular fractions. Changes in expression will be examined during development and with dietary and humoral status of the animal. Finally, we will attempt to determine the locus of the genetic defect in patients with glucose-galactose malabsorption syndrome.
| Kepe, Vladimir; Scafoglio, Claudio; Liu, Jie et al. (2018) Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas. J Neurooncol 138:557-569 |
| Paz, Aviv; Claxton, Derek P; Kumar, Jay Prakash et al. (2018) Conformational transitions of the sodium-dependent sugar transporter, vSGLT. Proc Natl Acad Sci U S A 115:E2742-E2751 |
| Gorraitz, Edurne; Hirayama, Bruce A; Paz, Aviv et al. (2017) Active site voltage clamp fluorometry of the sodium glucose cotransporter hSGLT1. Proc Natl Acad Sci U S A 114:E9980-E9988 |
| Ghezzi, Chiara; Yu, Amy S; Hirayama, Bruce A et al. (2017) Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal Tubule. J Am Soc Nephrol 28:802-810 |
| Sala-Rabanal, Monica; Hirayama, Bruce A; Ghezzi, Chiara et al. (2016) Revisiting the physiological roles of SGLTs and GLUTs using positron emission tomography in mice. J Physiol 594:4425-38 |
| Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka et al. (2016) Structural and functional significance of water permeation through cotransporters. Proc Natl Acad Sci U S A 113:E6887-E6894 |
| Adelman, Joshua L; Ghezzi, Chiara; Bisignano, Paola et al. (2016) Stochastic steps in secondary active sugar transport. Proc Natl Acad Sci U S A 113:E3960-6 |
| Gallo, Linda A; Wright, Ernest M; Vallon, Volker (2015) Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res 12:78-89 |
| Scafoglio, Claudio; Hirayama, Bruce A; Kepe, Vladimir et al. (2015) Functional expression of sodium-glucose transporters in cancer. Proc Natl Acad Sci U S A 112:E4111-9 |
| Adelman, Joshua L; Sheng, Ying; Choe, Seungho et al. (2014) Structural determinants of water permeation through the sodium-galactose transporter vSGLT. Biophys J 106:1280-9 |
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