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

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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.

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Acknowledgements

The authors are grateful to Celso Roberto Afonso for his excellent technical assistance and Carlos Henrique Fregadolli for their contribution to the statistical analyses.

Funding

This work was supported by the Brazilian foundation CAPES-Brasil (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil, Finance Code 001; PROCAD 160638) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant no. 308588/2016-9). This work is part of a dissertation presented by Chaiane Aline da Rosa as a partial requirement for a Master’s degree in Nutrition, Food and Metabolism at the College of Nutrition, UFMT.

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Authors and Affiliations

  1. Mestrado em Nutrição, Alimentos e Metabolismo, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil

    Chaiane Aline da Rosa-Santos, Priscila da Costa Rodrigues & Luana Resende Silva

  2. Departamento de Alimentos e Nutrição, Faculdade de Nutrição, Universidade Federal de Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367 Bairro Boa Esperança, Cuiabá, MT, 78060-900, Brazil

    Vanessa Cristina Arantes, Marise Auxiliadora de Barros Reis & Márcia Queiroz Latorraca

  3. Departamento de Clínica Médica Veterinária, Faculdade de Agronomia e Medicina Veterinária, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil

    Edson Moleta Colodel

  4. Departamento de Ciências Básicas da Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil

    Amílcar Sabino Damazo

  5. Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Egberto Gaspar de Moura

  6. Departamento de Anatomia, Biologia Celular, Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil

    Everardo Magalhães Carneiro

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  1. Chaiane Aline da Rosa-Santos
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  2. Priscila da Costa Rodrigues
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  3. Luana Resende Silva
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Correspondence to Márcia Queiroz Latorraca.

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da Rosa-Santos, C.A., da Costa Rodrigues, P., Silva, L.R. et al. Early protein restriction increases intra-islet GLP-1 production and pancreatic β-cell proliferation mediated by the β-catenin pathway. Eur J Nutr 59, 3565–3579 (2020). https://doi.org/10.1007/s00394-020-02192-6

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