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

氨基酸限制改变胰腺β细胞的生存机制:PI3K/Akt通路的可能作用

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

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.

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.

Conclusion

Amino acid restricted beta cell viability seems to be dependent on the PI3K/Akt pathway.

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.

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