According to the hypothesis that most glucose absorption occurs passively across intestinal tight junctions (paracellular absorption), one would predict fairly similar rates of in vivo absorption of L-glucose, the stereoisomer of D-glucose that is absorbed only passively and is not catabolized, and of 3-O-methyl-D-glucose (30MD-glucose), the D-glucose analogue that is actively and passively transported and not catabolized. In house sparrows Passer domesticus, we applied a pharmacokinetic method to measure simultaneous in vivo absorption of [C-14]L-glucose and [H-3]30MD-glucose in a situation in which intestinal glucose transporters were relatively saturated (gavage solution contained 200 mmol l(-1) 30MD-glucose). Fractional absorptions (F) were not significantly different between [H-3]30MD- and [C-14]L-glucose (0.80 vs 0.79), and the apparent rates of absorption did not differ significantly. When we performed the same experiment on other sparrows in a situation in which intestinal glucose transporters were relatively unsaturated (200 mmol l(1)(-) mannitol replaced 30MD-glucose in the gavage solution), the apparent rate of absorption was significantly reduced for [C-14]L-glucose by 39% and for [H-3]30MD-glucose by 26%. A simulation model showed that a reduction is not predicted if most of the [H-3]30MDglucose is actively absorbed, because the absorption rate of the tracer should increase when competitive inhibitor (unlabeled 30MD-glucose) is removed. The similar extent and rates of absorption of [H-3]30MD- and [C-14]L-glucose, and the acceleration of their rates of absorption in the presence of luminal 30MD-glucose, are most consistent with Pappenheimer's hypothesis that the majority of dietary D-glucose is absorbed passively.
