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Fig. 6. The simulated pattern of D- and L-glucose
radiolabeled probe absorption at the apical membrane in the presence of an
initial low substrate concentration (CC0=1 mmol
l-1) varies according to whether absorption is primarily mediated
or primarily passive. The initial probe concentration used in the modeling was
0.001 nmol µl-1 (i.e. tracer level). (A) Cumulative absorption
(%); (B) probe absorption rate. Four different situations are shown. (Ai,Bi)
Absorption described by kinetic values (Vmax,
Km and Ka) that have been measured
in vitro using isolated sparrow intestine
(Caviedes-Vidal and Karasov,
1996). We used the Vmax measured in that study
because in vitro rates of uptake of 3OMD-glucose and
D-glucose under saturating conditions were comparable
(Chang et al., 2004). (Aii,Bii)
Analogous to Ai,Bi but for the D-glucose analogue
3-O-methyl-D-glucose, which has lower affinity
(approximately 3x higher Km, determined in rats,
rabbits, guinea pigs and hamsters;
Jorgensen et al., 1961;
Syme and Levin, 1980;
Thomson et al., 1982).
(Aiii,Biii) Absorption based on the assumption that the
Vmax was underestimated in vitro due to handling
effects on tissue viability (Starck et
al., 2000), uses a 5x higher Vmax, and
thus represents absorption dominated by the mediated pathway. (Aiv,Biv)
Absorption based on the assumption that the Ka was
underestimated in vitro due to absence of solvent drag
(Pappenheimer, 1993), uses a
5x higher Ka, and thus represents absorption
dominated by the passive pathway. Notice that when passive absorption
dominates (Aiv,Biv) the predicted cumulative absorption of D- and
L-glucose probes as a function of time (Aiv) are much more similar
than when mediated absorption dominates (Aiii). Analogously, when passive
absorption dominates, the predicted absorption rates of D- and
L-glucose probes as a function of time (Biv) are much closer to
each other than when mediated absorption dominates (Biii).
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