학술논문

Early protein restriction increases intra-islet GLP-1 production and pancreatic β-cell proliferation mediated by the β-catenin pathway.
Document Type
Article
Source
European Journal of Nutrition. Dec2020, Vol. 59 Issue 8, p3565-3579. 15p. 3 Charts, 7 Graphs.
Subject
*CELL proliferation
*ANIMAL experimentation
*APOPTOSIS
*CELL physiology
*CELLULAR signal transduction
*CYTOSKELETAL proteins
*DIET in disease
*DIET therapy
*GLUCAGON
*INGESTION
*INTRAPERITONEAL injections
*ISLANDS of Langerhans
*DIETARY proteins
*RATS
*GLUCAGON-like peptide 1
*GLUCAGON-like peptide-1 agonists
Language
ISSN
1436-6207
Abstract
Purpose: In the present study, we investigated whether intra-islet GLP-1 production and its modulation have a role in apoptosis, proliferation or neogenesis that is compromised by protein restriction during the foetal and suckling periods. Methods: Exendin-4, a GLP-1 receptor agonist (treated groups), or saline (non-treated groups) was intraperitoneally administered for 15 days from 75 to 90 days of age in female adult rats consisting of offspring born to and suckled by mothers fed a control diet (control groups) and who had the same diet until 90 days of age or offspring born to and suckled by mothers fed a low-protein diet and who were fed the control diet after weaning until 90 days of age (protein-restricted group). Results: The β-cell mass was lower in the protein-restricted groups than in the control groups. Exendin-4 increased β-cell mass, regardless of the mother's protein intake. The colocalization of GLP-1/glucagon was higher in the protein-restricted rats than in control rats in both the exendin-4-treated and non-treated groups. The frequency of cleaved caspase-3-labelled cells was higher in the non-treated protein-restricted group than in the non-treated control group and was similar in the treated protein-restricted and treated control groups. Regardless of treatment with exendin-4, Ki67-labelled cell frequency and β-catenin/DAPI colocalization were elevated in the protein-restricted groups. Exendin-4 increased the area of endocrine cell clusters and β-catenin/DAPI and FoxO1/DAPI colocalization regardless of the mother's protein intake. Conclusions: Protein restriction in early life increased intra-islet GLP-1 production and β-cell proliferation, possibly mediated by the β-catenin pathway. [ABSTRACT FROM AUTHOR]