Amino acid restriction alters survival mechanisms in pancreatic beta cells: possible role of the PI3K/Akt pathway

Alves, Bruna Lourençoni; Araújo, Thiago dos Reis; Guimarães, Dimitrius Santiago Passos Simões Fróes; Zoppi, Cláudio Cesar; Figueiredo, Mariana Sarto; Carneiro, Everardo Magalhães

BACKGROUND AND AIMS: Malnutrition in the early stages of life may lead to changes in the glycemic metabolism during adulthood, such as pancreatic beta cells dysfunction and failure. Therefore, this study aimed to evaluate the effects of an in vitro amino acid restriction model on the function and viability of pancreatic beta cells. METHODS: Insulin-producing cells (INS-1E) were maintained in control or amino acid restricted culture medium containing 1 × or 0.25 × of amino acids, respectively, for 48 h. RESULTS: Amino acid restricted group showed lower insulin secretion and insulin gene expression, reduced mitochondrial oxygen consumption rate and reactive oxygen species production. Besides, amino acid restricted group also showed higher levels of endoplasmic reticulum stress and apoptosis markers and enhanced Akt phosphorylation. However, even with higher levels of apoptosis markers, amino acid restricted group did not show higher levels of cell death unless the PI3K/Akt pathway was inhibited. CONCLUSION: Amino acid restricted beta cell viability seems to be dependent on the PI3K/Akt pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02568-2.