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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #269434
Title: Glucagon-like peptide-2-stimulated protein synthesis through the PI 3-kinase-dependent Akt-mTOR signaling pathway

Author
item SHI, XUEMEI - Children'S Nutrition Research Center (CNRC)
item LI, XIAOJIE - Rio Grande Do Sul State Department Of Agricultural Research
item WANG, YI - Children'S Nutrition Research Center (CNRC)
item ZHANG, KEYING - China Agricultural University
item ZHOU, FUGUO - Sichuan University
item CHAN, LAWERENCE - China Agricultural University
item LI, DEFA - China Agricultural University
item GUAN, XINFU - Children'S Nutrition Research Center (CNRC)

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2010
Publication Date: 2/2/2011
Citation: Shi, X., Li, X., Wang, Y., Zhang, K., Zhou, F., Chan, L., Li, D., Guan, X. 2011. Glucagon-like peptide-2-stimulated protein synthesis through the PI 3-kinase-dependent Akt-mTOR signaling pathway. American Journal of Physiology - Endocrinology and Metabolism. 300(3):E554-E563.

Interpretive Summary: Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive gut hormone that exerts diverse actions in the gastrointestinal tract, including enhancing mucosal cell survival and proliferation. It is unclear whether GLP-2 can directly stimulate protein synthesis, the key metabolic process for cell proliferation. We showed that GLP-2 receptor activation directly stimulates protein synthesis. This finding is significant because GLP-2-stimulated protein synthesis may be physiologically relevant to its trophic action in mucosal growth and adaptation.

Technical Abstract: Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive neuropeptide that exerts diverse actions in the gastrointestinal tract, including enhancing mucosal cell survival and proliferation. GLP-2 stimulates mucosal growth in vivo with an increased rate of protein synthesis. However, it was unclear whether GLP-2 can directly stimulate protein synthesis. The objective was to test critically whether GLP-2 receptor (GLP-2R) activation directly stimulates protein synthesis through a PI 3-kinase-dependent Akt-mTOR signaling pathway. HEK 293 cells (transfected with human GLP-2R cDNA) were treated with human GLP-2 with/without pretreatment of PI 3-kinase inhibitor (LY-294002) or mTOR inhibitor (rapamycin). Results show that 1) GLP-2 specifically bound to GLP-2R overexpressed in the HEK cells with K(a) = 0.22 nM and B(max) = 321 fmol/µg protein; 2) GLP-2-stimulated protein synthesis was dependent on the amount of GLP-2R cDNA and the dosage of GLP-2 and reached the plateau among 0.2-2 nM GLP-2; 3) GLP-2-stimulated protein synthesis was abolished by the PI 3-kinase inhibitor and mTOR inhibitor; and 4) GLP-2-mediated stimulation of phosphorylation on Akt and mTOR was dependent on the amount of GLP-2R cDNA transfected and the dosage of GLP-2. In addition, GLP-2-mediated action and signaling in regulation of protein synthesis were confirmed in mouse hippocampal neurons (expressing native GLP-2R). GLP-2 directly stimulated protein synthesis of primary cultured neurons in dosage-dependent, PI 3-kinase-dependent, and rapamycin-sensitive manners, which linked with activation of Akt-mTOR signaling pathway as well. We conclude that GLP-2R activation directly stimulates protein synthesis by activating the PI 3-kinase-dependent Akt-mTOR signaling pathway. GLP-2-stimulated protein synthesis may be physiologically relevant to maintaining neuronal long-term potentiation and providing secondary mediators (namely neuropeptides or growth factors).