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United States Department of Agriculture

Agricultural Research Service

Title: Glucagon-like peptide-2 activates the mTOR signaling through a PI3-kinase-Akt-dependent pathway

Authors
item Li, Xiaojie - CHINA AGRICULTURAL UNIV
item Li, Defa - CHINA AGRICULTURAL UNIV
item Wang, Y - BAYLOR COLLEGE MED
item Qiao, Shiyan - CHINA AGRICULTURAL UNIV
item Chang, Benny - BAYLOR COLLEGE MED
item Burrin, Douglas
item Chan, Lawrence - BAYLOR COLLEGE MED
item Guan, Xinfu

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2007
Publication Date: April 1, 2007
Citation: Li, X., Li, D., Wang, Y., Qiao, S., Chang, B.H., Burrin, D.G., Chan, L., Guan, X. 2007. Glucagon-like peptide-2 activates the mTOR signaling through a PI3-kinase-Akt-dependent pathway [abstract]. Journal of Federation of American Societies for Experimental Biology. 21(6):A1075-A1076.

Technical Abstract: Glucagon-like peptide-2 (GLP-2) is nutrient-responsive neuropeptide that exerts diverse actions in the gastrointestinal tract. We have shown that GLP-2-stimulated mucosal growth occurred in vivo with an increased rate of protein synthesis in the neonatal intestine, which was associated with up-regulated phosphorylation of the Akt kinase. Evidence indicates that protein translation is controlled by the mammalian target of rapamycine (mTOR) signaling pathway. Thus, we hypothesized that GLP-2 receptor activation intracellularly stimulates the mTOR signaling through the phosphatidylinositol 3 (PI3)-kinase-Akt pathway. The HEK 293 cells were trasfected with a full-length cDNA of human GLP-2 receptor and treated with human GLP-2 with/without pre-treatment of a PI3-kinase inhibitor (LY294002). We found that GLP-2 dose-dependetly stimulated Akt phosphorylation at Ser473 and Thr308, which were suppressed by LY294002 at 60% and 30%, respectively. Moreover, GLP-2 stimulated mTOR phosphorylation at Ser2448, thus activating p70S6 kinase and inactivating the elF4E inhibitor (4E-BP1) by inducing phosphorylation of the p70S6 at Thr389 and the 4E-BP1 at Thr37/46, which were suppressed by LY294002 at 35% and 20%, respectively. We concluded that GLP-2-mediated activation of the mTOR signaling might be involved in GLP-2-stimulated mucosal protein synthesis, and was partially mediated by the PI3-kinase-Akt signaling pathway.

Last Modified: 12/27/2014
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