TY - JOUR
T1 - N-acetyl cysteine attenuates oxidative stress and glutathione-dependent redox imbalance caused by high glucose/high palmitic acid treatment in pancreatic Rin-5F cells
AU - Alnahdi, Arwa
AU - John, Annie
AU - Raza, Haider
N1 - Publisher Copyright:
© 2019 Alnahdi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Elevated levels of glucose and fatty acids are the main characteristics of diabetes, obesity and other metabolic disorders, associated with increased oxidative stress, mitochondrial dysfunction and inflammation. Once the primary pathogenesis of diabetes is established, which is potentially linked to both genetic and environmental factors, hyperglycemia and hyperlipidemia exert further destructive and/or toxic effects on β-cells. The concept of glucolipotoxicity has arisen from the combination of deleterious effects of chronic elevation of glucose and fatty acid levels on pancreatic β- cell function and/or survival. Though numerous studies have been conducted in this field, the exact molecular mechanisms and causative factors still need to be established. The aim of the present work was to elucidate the molecular mechanisms of oxidative stress, and inflammatory/antioxidant responses in the presence of high concentrations of glucose/fatty acids in a cell-culture system using an insulin-secreting pancreatic β-cell line (Rin-5F) and to study the effects of the antioxidant, N-acetyl cysteine (NAC) on β-cell toxicity. In our study, we investigated the molecular mechanism of cytotoxicity in the presence of high glucose (up to 25 mM) and high palmitic acid (up to 0.3 mM) on Rin-5F cells. Our results suggest that the cellular and molecular mechanisms underlying β-cell toxicity are mediated by increased oxidative stress, imbalance of redox homeostasis, glutathione (GSH) metabolism and alterations in inflammatory responses. Pretreatment with NAC attenuated oxidative stress and alterations in GSH metabolism associated with β-cells cytotoxicity.
AB - Elevated levels of glucose and fatty acids are the main characteristics of diabetes, obesity and other metabolic disorders, associated with increased oxidative stress, mitochondrial dysfunction and inflammation. Once the primary pathogenesis of diabetes is established, which is potentially linked to both genetic and environmental factors, hyperglycemia and hyperlipidemia exert further destructive and/or toxic effects on β-cells. The concept of glucolipotoxicity has arisen from the combination of deleterious effects of chronic elevation of glucose and fatty acid levels on pancreatic β- cell function and/or survival. Though numerous studies have been conducted in this field, the exact molecular mechanisms and causative factors still need to be established. The aim of the present work was to elucidate the molecular mechanisms of oxidative stress, and inflammatory/antioxidant responses in the presence of high concentrations of glucose/fatty acids in a cell-culture system using an insulin-secreting pancreatic β-cell line (Rin-5F) and to study the effects of the antioxidant, N-acetyl cysteine (NAC) on β-cell toxicity. In our study, we investigated the molecular mechanism of cytotoxicity in the presence of high glucose (up to 25 mM) and high palmitic acid (up to 0.3 mM) on Rin-5F cells. Our results suggest that the cellular and molecular mechanisms underlying β-cell toxicity are mediated by increased oxidative stress, imbalance of redox homeostasis, glutathione (GSH) metabolism and alterations in inflammatory responses. Pretreatment with NAC attenuated oxidative stress and alterations in GSH metabolism associated with β-cells cytotoxicity.
UR - http://www.scopus.com/inward/record.url?scp=85077015231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077015231&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0226696
DO - 10.1371/journal.pone.0226696
M3 - Article
C2 - 31860682
AN - SCOPUS:85077015231
SN - 1932-6203
VL - 14
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e0226696
ER -