Harry M. Vars Research Award. Influence of fasting on glutamine transport in rat liver

During starvation, the liver switches from an organ of net glutamine uptake to an organ of net glutamine release to help maintain blood glutamine levels. We hypothesized that this shift in hepatic glutamine exchange was regulated at the level of the hepatocyte plasma membrane by adaptive changes in glutamine transport. To test this hypothesis, adult rats (200 g) were allowed to consume regular rat food ad libitum (fed, n = 8) or were fasted for 72 hours (fasted, n = 8, access to water allowed). Livers were excised and hepatocyte plasma membrane vesicles were prepared by differential and Percoll density gradient centrifugation. Vesicle purity and functionality were assessed by marker enzyme measurements, classic "overshoots," and time courses, which showed similar vesicle size. Uptake of 3H-glutamine by hepatocyte plasma membrane vesicles in the presence and absence of sodium was assayed by a rapid mixing/filtration method, which reflects actual transport across the hepatocyte cell membrane in vivo. Fasted rats lost 15 +/- 2% of body weight; fed rats gained weight. Na(+)-dependent glutamine transport (system "N," mediates uptake into the hepatocyte) fell by 22% in the starved group, indicating a diminished rate of glutamine transport into the hepatocyte. In contrast, carrier-mediated Na(+)-independent glutamine transport (system "n," mediates the release of glutamine out of the cell) doubled in the starved animals. Diffusion of glutamine across the vesicle membrane was unchanged by starvation.(ABSTRACT TRUNCATED AT 250 WORDS)