title: Osmotic water transport with glucose in GLUT2 and SGLT.
abstract: Carrier-mediated water cotransport is currently a favored explanation for water movement against an osmotic gradient. The vestibule within the central pore of Na(+)-dependent cotransporters or GLUT2 provides the necessary precondition for an osmotic mechanism, explaining this phenomenon without carriers. Simulating equilibrative glucose inflow via the narrow external orifice of GLUT2 raises vestibular tonicity relative to the external solution. Vestibular hypertonicity causes osmotic water inflow, which raises vestibular hydrostatic pressure and forces water, salt, and glucose into the outer cytosolic layer via its wide endofacial exit. Glucose uptake via GLUT2 also raises oocyte tonicity. Glucose exit from preloaded cells depletes the vestibule of glucose, making it hypotonic and thereby inducing water efflux. Inhibiting glucose exit with phloretin reestablishes vestibular hypertonicity, as it reequilibrates with the cytosolic glucose and net water inflow recommences. Simulated Na(+)-glucose cotransport demonstrates that active glucose accumulation within the vestibule generates water flows simultaneously with the onset of glucose flow and before any flow external to the transporter caused by hypertonicity in the outer cytosolic layers. The molar ratio of water/glucose flow is seen now to relate to the ratio of hydraulic and glucose permeability rather than to water storage capacity of putative water carriers.
authors.affiliation: King's College London, Physiology, Waterloo Campus, London SE1 9HN, United Kingdom. richard.naftalin@kcl.ac.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Naftalin
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D005947:Glucose / Q000737:chemistry*; D051273:Glucose Transporter Type 2 / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D009997:Osmotic Pressure; D011312:Pressure; D011487:Protein Conformation; D051247:Sodium-Glucose Transport Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D014867:Water / Q000737:chemistry*
chemical_list: D051273:Glucose Transporter Type 2; D051247:Sodium-Glucose Transport Proteins; D014867:Water; D005947:Glucose