Imagine that you are investigating the transepithelial transport of radioactive glucose. Intestinal epithelial cells are grown in culture to form a complete sheet so that the fluid bathing the apical domain of the cells (the apical medium) is completely separated from the fluid bathing the basolateral domain of the cells (the basolateral medium). Radioactive e4 C-Iabeled) glucose is added to the apical medium, and the appearance of radioactivity in the basolateral medium is monitored in terms of counts per minute per milliliter (cpm/ml), a measure of radioactivity per unit volume.

Treatment 1: The apical and basolateral media each contain 150 mM Na⁺ (curve 1).

Treatment 2: The apical medium contains 1 mM Na, and the basolatcral medium contains 150 mM Na⁺ (curve 2).

Treatment 3: The apical medium contains 150 mM Na, and the basolateral medium contains I mM Na ⁺ (curve 3).

a. What is a likely explanation for the different results obtained in treatments 1 and 3 versus treatment 2?

In additional studies, the drug ouabain, which inhibits Na ⁺/K⁺ ATPases, is included as noted.

Treatment 4: The apical and basolateral media contain 150 mM Na⁺ and the apical media contains ouabain (curve 4).

Treatment 5: The apical and basolateral media contain 150 mM Na⁺ and the basolatcral media contains ouabain (curve 5).

b. What is a likely explanation for the different results obtained in treatment 4 versus treatment 5?

c. Certa in natural compounds and drugs being tested as treatments for diabetes lower glucose transport in intestinal or kidney epithelial cell s, and thereby lower blood sugar levels. Addition of one such drug to the apical medium yields transport similar to that in Treatment 5, whereas its addition to the basolateral medium yields transport similar to that in Treatment 4. What is the most likely target of this drug, and what is the effect on this target?

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Radioactivity in Basolateral Medium 200 Treatments 1, 3 150 100 50 Treatment 2 8. 10 Time (min) in 14C-glucose Radioactivity (cpm/ml) Radioactivity in Basolateral Medium 200 Treatment 4 150 100 50 Treatment 5 8. 10 Time (min) in 14C-glucose Radioactivity (cpm/ml)