title: A Mechanistic Study on Nanoparticle-Mediated Glucagon-Like Peptide-1 (GLP-1) Secretion from Enteroendocrine L Cells.
abstract: L cells have attracted particular interest because of the pleiotropic effects of their secreted peptides (i.e., glucagon-like peptide (GLP) 1 and 2, peptide YY (PYY)). L cells express different G-protein-coupled receptors (GPCRs) that can be activated by endogenous ligands found in the gut lumen. We herein hypothesized that lipid-based nanoparticles could mimic endogenous ligands and thus activate GLP-1 secretion in type 2 diabetes mellitus treatment. To assess this hypothesis, lipid-based nanoparticles (nanostructured lipid carriers (NLC), lipid nanocapsules (LNC), and liposomes) and PLGA nanoparticles were added to the L cells and GLP-1 secretion was quantified. Among these nanoparticles, only NLC resulted effective at inducing GLP-1 secretion in both murine and human L cells in vitro. The mRNA expression of proglucagon showed that this effect was due to an increased GLP-1 secretion and not to an increased GLP-1 synthesis. The mechanism by which NLC triggered GLP-1 secretion by L cells revealed an extracellular interaction of NLC, exerting a physiological GLP-1 secretion. We herein demonstrate that nanomedicine can be used to induce GLP-1 secretion from murine and human L cells.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute , Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Ana
authors.initials: A
authors.lastname: Beloqui
authors.affiliation: Université catholique de Louvain , Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Group, 1200 Brussels, Belgium.
authors.forename: Mireille
authors.initials: M
authors.lastname: Alhouayek
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute , Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Dario
authors.initials: D
authors.lastname: Carradori
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute , Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Vanvarenberg
authors.affiliation: Université catholique de Louvain , Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Group, 1200 Brussels, Belgium.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.affiliation: Université catholique de Louvain , WELBIO (Walloon Excellence in Life sciences and BIOtechnology), Louvain Drug Research Institute, Metabolism and Nutrition Group, 1200 Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute , Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019858:Enteroendocrine Cells / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D008055:Lipids; D052216:Glucagon-Like Peptide 1
keywords: GLP-1; L cells; enteroendocrine system; incretin; type 2 diabetes mellitus