L-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK.
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abstract
Neonates (including human infants) require L-glutamine (Gln) for optimal intestinal health. This study tested the hypothesis that Gln enhances enterocyte growth via both mammalian target of rapamycin (mTOR) and AMP-activated kinase (AMPK) signaling pathways. Intestinal porcine epithelial cells (IPEC-1) were cultured for 3days in Gln-free Dulbecco's modified Eagle medium containing 0 or 2mM Gln. To determine the role of mTOR and AMPK on cell growth, additional experiments were conducted where medium contained 2mM Gln and 10nM rapamycin (Rap, an inhibitor of mTOR) or 1M compound C (an inhibitor of AMPK). IPEC-1 cell growth increased with increasing concentrations of Gln from 0 to 2mM. Compared with 0mM Gln, 2mM Gln increased (P<0.05) the amounts of phosphorylated 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6 kinase) proteins but did not affect abundances of total or phosphorylated AMPK protein. Gln also increased mRNA levels for Bcl-2, mTOR, p70S6 kinase, 4E-BP1, COX7C, ASCT2, ODC, SGLT-1, CFTR, Na(+)/K(+)-ATPase, HSP70, and ZO-1. Similarly, cells cultured with Rap and Gln exhibited higher (P<0.05) abundances of phosphorylated 4E-BP1 and p70S6 kinase proteins than the Rap-only group, whereas abundances of phosphorylated mTOR and 4E-BP1 proteins were increased when AMPK was inhibited by compound C. Conversely, the amount of phosphorylated AMPK increased when mTOR was inhibited by Rap, suggesting a negative cross-talk between mTOR and AMPK. Collectively, these results indicate that Gln stimulates enterocyte growth by activating the mTOR signaling pathway independently of AMPK.
