Jejunal epithelial glucose metabolism: Effects of Na⁺ replacement

The objective of this study was to characterize the effects of replacement of extracellular Na⁺ with a nontransportable cation, N-methyl-D-glucamine (NMDG⁺) on jejunal epithelial glucose metabolism. Jejunal epithelium isolated from male Sprague-Dawley rats was incubated in media containing 5 mM glucose, 0.5 mM glutamine, 0.5 mM β-hydroxybutyrate, and 0.3 mM acetoacetate as the principal carbon sources. O₂ consumption and total glucose utilization were reduced 30 and 50%, respectively, when Na⁺ was replaced with NMDG⁺. In both media, ~75% of utilized glucose carbon was converted to lactate. The rate of glucose metabolism via the hexose monophosphate shunt, as evaluated using specific ¹⁴CO₂ yields from [1-¹⁴C]glucose and [6-¹⁴C]glucose, was not appreciably altered by Na⁺ replacement. Tricarboxylic acid (TCA) cycle flux was evaluated using ¹⁴CO₂ production from [¹⁴C]glucose and [¹⁴C] pyruvate radioisotopes. Approximately 50% of TCA cycle flux was shunted into products other than CO₂ in both media. The majority of the actyl-CoA oxidized in the TCA cycle was derived from cytosolic pyruvate. It is concluded that removal of Na⁺ from the bathing medium substantially reduced glucose utilization via the Embden-Meyerhof pathway and TCA cycle in the jejunal epithelium.