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.

scholarly journals Glucose-Dependent Changes in SNARE Protein Levels in Pancreatic β-Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1290-1299 ◽  
Author(s):  
Benjamín Torrejón-Escribano ◽  
Jessica Escoriza ◽  
Eduard Montanya ◽  
Juan Blasi
Keyword(s):  
Insulin Secretion ◽  
Protein Expression ◽  
High Glucose ◽  
Glucose Concentration ◽  
Snare Proteins ◽  
High Glucose Concentration ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
In Vivo Models ◽  
Insulin Granule

Abstract Prolonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic β-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo models (cultured rat pancreatic islets incubated in high glucose media, partially pancreatectomized rats, and islets transplanted to streptozotozin-induced diabetic mice) were used to evaluate the dependence of the biological model and the treatment, together with the cell location (insulin granule or plasma membrane) of the affected proteins and the possible effect of sustained insulin secretion, on the glucose-induced changes in protein expression. In all three models, islets exposed to high glucose concentrations showed a reduced expression of secretory granule-associated vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin/vesicle-associated membrane protein 2 and cellubrevin but minor or no significant changes in the expression of the membrane-associated target-SNARE proteins syntaxin1 and synaptosomal-associated protein-25 and a marked increase in the expression of synaptosomal-associated protein-23 protein. The inhibition of insulin secretion by the L-type voltage-dependent calcium channel nifedipine or the potassium channel activator diazoxide prevented the glucose-induced reduction in islet insulin content but not in vesicle-SNARE proteins, indicating that the granule depletion due to sustained exocytosis was not involved in the changes of protein expression induced by high glucose concentration. Altogether, the results suggest that high glucose has a direct toxic effect on the secretory pathway by decreasing the expression of insulin granule SNARE-associated proteins.

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 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

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.

Crucial roles of neuronatin in insulin secretion and high glucose-induced apoptosis in pancreatic β-cells

2008 ◽  
Vol 20 (5) ◽  
pp. 907-915 ◽  
Author(s):  
Myung Kuk Joe ◽  
Hyo Jung Lee ◽  
Young Ho Suh ◽  
Kyu Lee Han ◽  
Joo Hyun Lim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
High Glucose ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Induced Apoptosis

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.

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