Amino acid restriction increases β-cell death under challenging conditions

Journal of Cellular Physiology
Luciana Mateus GonçalvesEverardo Magalhães Carneiro

Abstract

Malnutrition programs metabolism, favor dysfunction of β cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the β cells. Insulin-producing cells INS-1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of β-cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho-eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed β cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with β-cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition.

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Citations

Apr 30, 2021·European Journal of Nutrition·Bruna Lourençoni AlvesEverardo Magalhães Carneiro

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis