A Mechanistic Study on Nanoparticle-Mediated Glucagon-Like Peptide-1 (GLP-1) Secretion from Enteroendocrine L Cells

被引：33

作者：

Beloqui, Ana ^{[1
]}

Alhouayek, Mireille ^{[2
]}

Carradori, Dario ^{[1
]}

Vanvarenberg, Kevin ^{[1
]}

Li, Giulio G. Mucci ^{[2
]}

Cani, Patrice D. ^{[3
]}

Preat, Veronique ^{[1
]}

机构：

[1] Catholic Univ Louvain, Louvain Drug Res Inst, Adv Drug Delivery & Biomat, Ave Mounier 73 Box B1 73-12, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, Louvain Drug Res Inst, Bioanal & Pharmacol Bioact Lipids Grp, B-1200 Brussels, Belgium

[3] Catholic Univ Louvain, WELBIO Walloon Excellence Life Sci & BIOtechnol, Louvain Drug Res Inst, Metab & Nutr Grp, B-1200 Brussels, Belgium

来源：

MOLECULAR PHARMACEUTICS | 2016年 / 13卷 / 12期

关键词：

L cells; type 2 diabetes mellitus; enteroendocrine system; GLP-1; incretin; NANOSTRUCTURED LIPID CARRIERS; CHAIN FATTY-ACIDS; GUT MICROBIOTA; ORAL DELIVERY; INFLAMMATION; GPR119; TRANSPORT; CURCUMIN; AGONISTS;

D O I：

10.1021/acs.molpharmaceut.6b00871

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页码：4222 / 4230

页数：9

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Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6 [J].