Owing to the uncertainties of transport kinetics, the mechanism of glucose transport via GLUT1 remains unclear, however extended atomistic molecular dynamics simulations of GLUT1 embedded in a  symmetrical bilayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)  in the fluid state  at 323.15 K, or in the  gel  state at 308.15 K, surrounded by a physiological salt solution have resolved some ambiguities. An outstanding question is: does net glucose transport require conformational changes that alternately  expose the central high affinity ligand binding site to externally and internally facing solutions; or does glucose transit by random jumps between adjacent sites, aided by small fluctuations  that intermittently open and close the tunnels and cavities along the central cleft? By using a “flooding protocol,”  equivalent to 50 mM glucose, in comparison with another without glucose,  atomistic molecular dynamics simulations reveal a large number  of amino acids,  whose fluctuations alter with raised glucose concentration.   Both protocols are applied to the fluid and gel membrane states:  the gel  state reduces  transporter fluctuations [1].   The glucose-dependent changes are most evident in the extra-membranous zones.   In the fluid state, during  2 µs simulations, these glucose-amplified fluctuations permit glucose and water permeation from both external and cytosolic solutions along the length of the central pore.   However, in the gel state, glucose penetration is confined to the extramembranous regions.      With increasing glucose proximity  (< 5 Ǻ) to the bottlenecks that normally occlude the internal and external openings of GLUT1’s central pore, the frequency of opening events increases by 2-20-fold.   These bottlenecks are formed by  hydrophobic side chains, held together by van der Waals interactions.  Rotamer changes  occasionally alter the minimal external bottleneck radius from ≈ 1.0 Ǻ to 2.2 Ǻ and at the internal barrier from 1.2 Ǻ  to 2.3 Ǻ.  Thus,  close  glucose proximity  allows spontaneous unsteered glucose flows through these apertures.  No  glucose penetration into the intramembranous regions occurs in the gel state.      Furthermore,  in the fluid flooded state,  glucose proximity (< 6 Ǻ), increases the probability of wider separations occurring in 12/17 salt bridges between lysine or arginine and glutamate or aspartate within the extramembranous loops. Glucose-dependent opening of the extramembranous tunnels in the fluid-flooded condition  permits several observed glucose traversals through the GLUT1’s central region, considered to be the high affinity binding site, without any large accompanying transmembrane helical conformation changes.   This structural expansion  caused by multiple simultaneous H-bonding interactions between glucose and GLUT1 accounts for the higher spontaneous intramolecular glucose mobility seen in these simulations than with any reported previously.     These findings are  consistent with the temperature sensitivity of glucose transport seen in reconstituted lipid  DPPC vesicles [2] and in human erythrocytes [3] and the glucose-dependent decrease in activation energy of L-sorbose transport across human erythrocyte GLUT1(4).