Size Effect on Lipid Nanocapsule-Mediated GLP-1 Secretion from Enteroendocrine L Cells

Mol Pharm. 2018 Jan 2;15(1):108-115. doi: 10.1021/acs.molpharmaceut.7b00742. Epub 2017 Dec 15.


L cells are enteroendocrine cells located throughout the gastrointestinal tract that secrete physiologically important peptides. The most characterized peptides secreted by L cells are the peptide YY (PYY) and the glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). These peptides are released rapidly into the circulation after oral nutrient ingestion. Recently, lipid-based nanoparticles (NP) have been described as triggers for GLP-1 secretion by L cells. NP physicochemical properties play a key role in the NP-cell interaction, and drive NP cell internalization. We herein hypothesize that lipid-based NP with appropriate size would not only be able to deliver drugs into blood circulation but also act like endogenous ligands to stimulate GLP-1 secretion. We tested five different size (25, 50, 100, 150, and 200 nm) lipid nanocapsules (LNC) on murine L cells in vitro to confirm this hypothesis. Our study showed that GLP-1 secretion was induced only by the 200 nm size LNC, highlighting the importance of LNC particle size on the secretion of GLP-1 by L cells. The different formulations did not affect proglucagon mRNA expression, suggesting that there was not an increased GLP-1 synthesis. As a proof of concept, we further demonstrated in normoglycemic mice that 200 nm LNC administration increases GLP-1 levels by 4- and 3-fold compared to untreated control mice 60 and 180 min after the administration, respectively. Our study suggests that 200 nm LNC as a nanocarrier to encapsulate drug candidates and as a ligand to induce endogenous GLP-1 secretion might represent a promising strategy for type 2 diabetes mellitus treatment.

Keywords: GLP-1; enteroendocrine L cells; incretin; lipid nanocapsules; size effect; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / physiology
  • Diabetes Mellitus, Type 2
  • Enteroendocrine Cells / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Incretins / metabolism
  • Lipids / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Nanocapsules / chemistry*


  • Incretins
  • Lipids
  • Nanocapsules
  • Glucagon-Like Peptide 1