scholarly journals Mitochondria-targeted Antioxidants Protect Pancreatic β-cells against Oxidative Stress and Improve Insulin Secretion in Glucotoxicity and Glucolipotoxicity

2011 ◽  
Vol 28 (5) ◽  
pp. 873-886 ◽  
Author(s):  
Sangbin Lim ◽  
Md Abdur Rashid ◽  
Miran Jang ◽  
Yeonghwan Kim ◽  
Hyeran Won ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Cytoprotective Effects of N-Acetylcysteine on Streptozotocin- Induced Oxidative Stress and Apoptosis in RIN-5F Pancreatic β-Cells

2018 ◽  
Vol 51 (1) ◽  
pp. 201-216 ◽  
Author(s):  
Arwa M.T. Al-Nahdi ◽  
Annie John ◽  
Haider  Raza
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Molecular Mechanisms ◽  
Protective Action ◽  
Mitochondrial Enzymes ◽  
Partial Recovery ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Energy Metabolism ◽  
Mitochondrial Functions

Background/Aims: Numerous studies have reported overproduction of reactive oxygen species (ROS) and alterations in mitochondrial energy metabolism in the development of diabetes and its complications. The potential protective effects of N-acetylcysteine (NAC) in diabetes have been reported in many therapeutic studies. NAC has been shown to reduce oxidative stress and enhance redox potential in tissues protecting them against oxidative stress associated complications in diabetes. In the current study, we aimed to investigate the molecular mechanisms of the protective action of NAC on STZ-induced toxicity in insulin secreting Rin-5F pancreatic β-cells. Methods: Rin-5F cells were grown to 80% confluence and then treated with 10mM STZ for 24h in the presence or absence of 10mM NAC. After sub-cellular fractionation, oxidative stress, GSH-dependent metabolism and mitochondrial respiratory functions were studied using spectrophotometric, flow cytometric and Western blotting techniques. Results: Our results showed that STZ-induced oxidative stress and apoptosis caused inhibition in insulin secretion while NAC treatment restored the redox homeostasis, enhanced insulin secretion in control cells and prevented apoptosis in STZ-treated cells. Moreover, NAC attenuated the inhibition of mitochondrial functions induced by STZ through partial recovery of the mitochondrial enzymes and restoration of membrane potential. STZ-induced DNA damage and expression of apoptotic proteins were significantly inhibited in NAC-treated cells. Conclusion: Our results suggest that the cytoprotective action of NAC is mediated via suppression of oxidative stress and apoptosis and restoration of GSH homeostasis and mitochondrial bioenergetics. This study may, thus, help in better understanding the cellular defense mechanisms of pancreatic β-cells against STZ-induced cytotoxicity.

scholarly journals Protective Effect of Siegesbeckia orientalis on Pancreatic β-Cells under High Glucose-Induced Glucotoxicity

2021 ◽  
Vol 11 (22) ◽  
pp. 10963
Author(s):  
Chi-Chang Chang ◽  
Jer-Yiing Houng ◽  
Shih-Wei Wang ◽  
Chin-Feng Hsuan ◽  
Yung-Chuan Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Insulin Secretion ◽  
Protective Effect ◽  
Normal Level ◽  
High Glucose ◽  
Glucose Concentration ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Siegesbeckia Orientalis

The glucotoxicity caused by long-term exposure of β-cells to high glucose (HG) conditions may lead to the generation of more reactive oxygen species (ROS), reduce the activity of antioxidant enzymes, cause cell damage and apoptosis, and induce insulin secretion dysfunction. Siegesbeckia orientalis linne is a traditional folk herbal medicine used to treat snake bites, rheumatoid arthritis, allergies, and immune deficiencies. In this study, we evaluated the protective effect of S. orientalis ethanol extract (SOE) on cell death and oxidative stress in RIN-m5f pancreatic β-cells stimulated by two HG concentrations (50–100 mM). In the cell viability assay, SOE could significantly increase the survival rate of pancreatic β-cells under HG-induced conditions. For the oxidative stress induced by HG condition, the treatment of SOE effectively reduced the ROS formation, increased the content of intracellular glutathione, and up-regulated the expression of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase. As a result, the SOE treatment could decrease the glucotoxicity-mediated oxidative damage on RIN-m5F β-cells. Moreover, SOE had the function of regulating insulin secretion in pancreatic β-cells under different HG-mediated conditions. It could decrease the increasing intracellular insulin secretion under the low glucose concentration to normal level; while increase the decreasing intracellular insulin secretion under the relatively high glucose concentration to normal level. Taken together, this study suggests that SOE has a protective effect on pancreatic β-cells under the HG-stimulated glucotoxic environment.

CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response

2016 ◽  
Vol 310 (3) ◽  
pp. E200-E212 ◽  
Author(s):  
Thierry Ntimbane ◽  
Geneviève Mailhot ◽  
Schohraya Spahis ◽  
Remi Rabasa-Lhoret ◽  
Marie-Laure Kleme ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Insulin Secretion ◽  
Inflammatory Responses ◽  
Lipid Peroxides ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Min6 Cells ◽  
Atp Production

Cystic fibrosis (CF)-related diabetes (CFRD) has become a critical complication that seriously affects the clinical outcomes of CF patients. Although CFRD has emerged as the most common nonpulmonary complication of CF, little is known about its etiopathogenesis. Additionally, whether oxidative stress (OxS), a common feature of CF and diabetes, influences CFRD pathophysiology requires clarification. The main objective of this study was to shed light on the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in combination with OxS in insulin secretion from pancreatic β-cells. CFTR silencing was accomplished in MIN6 cells by stable expression of small hairpin RNAs (shRNA), and glucose-induced insulin secretion was evaluated in the presence and absence of the valuable prooxidant system iron/ascorbate (Fe/Asc; 0.075/0.75 mM) along with or without the antioxidant Trolox (1 mM). Insulin output from CFTR-silenced MIN6 cells was significantly reduced (∼70%) at basal and at different glucose concentrations compared with control Mock cells. Furthermore, CFTR silencing rendered MIN6 cells more sensitive to OxS as evidenced by both increased lipid peroxides and weakened antioxidant defense, especially following incubation with Fe/Asc. The decreased insulin secretion in CFTR-silenced MIN6 cells was associated with high levels of NF-κB (the major participant in inflammatory responses), raised apoptosis, and diminished ATP production in response to the Fe/Asc challenge. However, these defects were alleviated by the addition of Trolox, thereby pointing out the role of OxS in aggravating the effects of CFTR deficiency. Our findings indicate that CFTR deficiency in combination with OxS may contribute to endocrine cell dysfunction and insulin secretion, which at least in part may explain the development of CFRD.

scholarly journals Effect of dietary oxidized tyrosine products on insulin secretion via the oxidative stress-induced mitochondria damage in mice pancreas

RSC Advances ◽  
2017 ◽  
Vol 7 (43) ◽  
pp. 26809-26826 ◽  
Author(s):  
Yin-Yi Ding ◽  
Xiang-Rong Cheng ◽  
Zhu-Qing Li ◽  
Sha-Ji Wu ◽  
Yuhui Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Mitochondrial Damage ◽  
Β Cells ◽  
Pancreatic Β Cells

The findings suggested that decreased insulin secretion triggered by OTPs may be mediated by oxidative stress and mitochondrial damage in pancreatic β cells.

scholarly journals GLP1-derived nonapeptide GLP1(28–36)amide protects pancreatic β-cells from glucolipotoxicity

2012 ◽  
Vol 213 (2) ◽  
pp. 143-154 ◽  
Author(s):  
Zhengu Liu ◽  
Violeta Stanojevic ◽  
Luke J Brindamour ◽  
Joel F Habener
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Islet Cells ◽  
Blood Levels ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Cell Functions

Type 2 diabetes, often associated with obesity, results from a deficiency of insulin production and action manifested in increased blood levels of glucose and lipids that further promote insulin resistance and impair insulin secretion. Glucolipotoxicity caused by elevated plasma glucose and lipid levels is a major cause of impaired glucose-stimulated insulin secretion from pancreatic β-cells, due to increased oxidative stress, and insulin resistance. Glucagon-like peptide-1 (GLP1), an insulinotropic glucoincretin hormone, is known to promote β-cell survival via its actions on its G-protein-coupled receptor on β-cells. Here, we report that a nonapeptide, GLP1(28–36)amide, derived from the C-terminal domain of the insulinotropic GLP1, exerts cytoprotective actions on INS-1 β-cells and on dispersed human islet cells in vitro in conditions of glucolipotoxicity and increased oxidative stress independently of the GLP1 receptor. The nonapeptide appears to enter preferably stressed, glucolipotoxic cells compared with normal unstressed cells. It targets mitochondria and improves impaired mitochondrial membrane potential, increases cellular ATP levels, inhibits cytochrome c release, caspase activation, and apoptosis, and enhances the viability and survival of INS-1 β-cells. We propose that GLP1(28–36)amide might be useful in alleviating β-cell stress and might improve β-cell functions and survival.

Citrus flavanone metabolites protect pancreatic-β cells under oxidative stress induced by cholesterol

2020 ◽  
Vol 11 (10) ◽  
pp. 8612-8624
Author(s):  
Sara L. Anacleto ◽  
Dragan Milenkovic ◽  
Paul A. Kroon ◽  
Paul W. Needs ◽  
Franco Maria Lajolo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Antioxidant Properties ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Oxidative Biomarkers

Flavanone metabolites decreased the oxidative biomarkers and this effect might be associated with the anti-apoptotic and antioxidant properties of these compounds as well their ability to prevent mitochondrial and insulin secretion dysfunction.

Glucolipotoxicity-induced oxidative stress is related to mitochondrial dysfunction and apoptosis of pancreatic β-cell

2020 ◽  
Vol 16 ◽  
Author(s):  
Jorge E. Vela-Guajardo ◽  
Salvador Garza-González ◽  
Noemí García
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Insulin Secretion ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Atp Synthesis ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Diabetes Development

: Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic β-cells are one of the mechanisms that have been related to the low insulin secretion and cell death during diabetes development. In early or non-chronic stages, the pancreatic β-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion. However, the chronic effect of both leads to the establishment of glucolipotoxicity which induces constant overstimulation of pancreatic β-cells, a condition that leads to cell death by apoptosis. The mechanism described, at this moment, is the accelerated mitochondrial dysfunction triggered by the high production of reactive oxygen species (ROS) due to excess nutrients. At first, mitochondria respond to over-nutrition accelerating oxygen consumption and consequently increasing the ATP synthesis. A permanent increase of ATP/ADP ratio leads to a constant inhibition of K+ ATP-channel and therefore a continuous insulin secretion accompanied by an increase in ROS. Finally, ROS accumulation compromises mitochondrial function due to the uncontrolled oxidation of proteins, lipids, and DNA generating functional alterations such as a drop of membrane potential, deregulation of mitochondrial dynamics, low rate of ATP synthesis and consequently the cell death. This review aims to describe the effect of glucolipotoxicity-induced oxidative stress and its relationship with mitochondrial dysfunction in β-cell during type 2 diabetes development.

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