A Mechanistic Study on Nanoparticle-Mediated Glucagon-Like Peptide-1 (GLP-1) Secretion from Enteroendocrine L Cells.
(2016) Molecular Pharmaceutics — Vol. 13, n° 12, p. 4222-4230 (2016)
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- 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.
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Beloqui Garcia, A., Al Houayek, M., Carradori, D., Vanvarenberg, K., Muccioli, G., Cani, P., & Préat, V. (2016). A Mechanistic Study on Nanoparticle-Mediated Glucagon-Like Peptide-1 (GLP-1) Secretion from Enteroendocrine L Cells. Molecular Pharmaceutics, 13(12), 4222-4230. https://doi.org/10.1021/acs.molpharmaceut.6b00871 (Original work published 2016)