Early protein restriction increases intra-islet GLP-1 production and pancreatic β-cell proliferation mediated by the β-catenin pathway

• Published in: European journal of nutrition Vol. 59; no. 8; pp. 3565 - 3579
• Main Authors: da Rosa-Santos, Chaiane Aline, da Costa Rodrigues, Priscila, Silva, Luana Resende, Arantes, Vanessa Cristina, de Barros Reis, Marise Auxiliadora, Colodel, Edson Moleta, Damazo, Amílcar Sabino, de Moura, Egberto Gaspar, Carneiro, Everardo Magalhães, Latorraca, Márcia Queiroz
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2020; Springer Nature B.V
• Subjects: Age; Apoptosis; Beta cells; Caspase-3; Cell growth; Cell proliferation; Chemistry; Chemistry and Materials Science; FOXO1 protein; Glucagon; Kinases; Low protein diet; Nutrient deficiency; Nutrition; Offspring; Original Contribution; Pancreas; Proteins; Suckling behavior; Weaning; β-Catenin; Early protein restriction; β-Catenin; β-Cell proliferation; Islets; GLP-1; Exendin-4
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-020-02192-6

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.