Size Effect on Lipid Nanocapsule-Mediated GLP-1 Secretion from Enteroendocrine L Cells
MOLECULAR PHARMACEUTICS
Authors: Xu, Yining; Carradori, Dario; Alhouayek, Mireille; Muccioli, Giulio G.; Cani, Patrice D.; Preat, Veronique; Beloqui, Ana
Abstract
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.
Effects of dietary protein levels on activities of protease and expression of ingestion and protein digestion-related genes in Nile tilapia juveniles
AQUACULTURE RESEARCH
Authors: Santos, Welliene M.; Costa, Leandro S.; Lopez-Olmeda, Jose F.; Costa, Natalia Cristina S.; Santos, Fabio A. C.; Gamarano, Pedro G.; Silva, Walisson S.; Rosa, Priscila, V; Luz, Ronald K.; Ribeiro, Paula A. P.
Abstract
While some studies have investigated the effects of dietary protein on the activities of protease in Nile tilapia, little information exists about these enzymes and hormones regulating appetite at the molecular level. Therefore, we investigated the performance, protease activities and expression of genes related to protein intake and digestion in juvenile tilapia fed with diets containing different levels of crude protein (CP): 25.14, 31.12, 36.60 and 42.05%. The fish were fed to apparent satiation three times a day for 65 days. The animal performance and the retention rates of protein and energy linearly decreased with an increase in dietary CP content. A positive quadratic effect of CP on pepsinogen was observed, although the acid protease activity was not affected. Trypsinogen and trypsin activity in the intestine presented similar patterns, showing a positive quadratic response to dietary protein levels. A linear increase in intestinal chymotrypsinogen expression was observed, but the activity of chymotrypsin showed a positive quadratic response. In addition, the expression of cholecystokinin (cck) and peptide yy (pyy) increased linearly with increasing CP. Dietary protein modulates the activity of alkaline proteases as well as the expression of these protease genes and hormones involved in appetite regulation. These changes can help expand our understanding of feed intake and digestion control, thereby improving feed formulations for this species.