Taurine Supplementation Restores Insulin Secretion and Reduces ER Stress Markers in Protein-Malnourished Mice
Endoplasmic reticulum (ER) stress is a cellular response to increased intra-reticular protein accumulation or poor ER function. Chronic activation of this pathway may lead to beta cell death and metabolic syndrome (MS). Poor nutrition during perinatal period, especially protein malnutrition, is associated with increased risk for MS in later life. Here, we analyzed the effects of taurine (TAU) supplementation upon insulin secretion and ER stress marker expression in pancreatic islets and in the liver from mice fed a low-protein diet. Malnourished mice had lower body weight and plasma insulin. Their islets secreted less insulin in response to stimulatory concentrations of glucose. TAU supplementation increased insulin secretion in both normal protein and malnourished mice. Western blot analysis revealed lower expression of the ER stress markers CHOP and ATF4 and increased phosphorylation of the survival protein Akt in pancreatic islets of TAU-supplemented mice. The phosphorylation of the mitogenic protein extracellular signal-regulated kinase (ERK1/2) was increased after acute incubation with TAU. Finally, the ER stress markers p-PERK and BIP were increased in the liver of malnourished mice and TAU supplementation normalized these parameters.
In conclusion, malnutrition leads to impaired islet function which is restored with TAU supplementation possibly by increasing survival signals and lowering ER stress proteins. Lower ER stress markers in the liver may also contribute to the improvement of insulin action on peripheral organs.
KeywordsBeta Cell Endoplasmic Reticulum Stress Pancreatic Islet Endoplasmic Reticulum Stress Marker Reduce Endoplasmic Reticulum Stress
Activating transcription factor 4
Binding immunoglobulin protein
C/EBP homologous protein
Extracellular signal-regulated kinase
PKR-like ER kinase
Sarco(endo)plasmic reticulum Ca2+-ATPase
This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq), and Instituto Nacional de Ciência e Tecnologia (INCT).
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