Molecular aspects of pancreatic β‐cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA

2018 ◽  
Vol 234 (6) ◽  
pp. 8411-8425 ◽  
Author(s):  
Mohammad Javad Saeedi Borujeni ◽  
Ebrahim Esfandiary ◽  
Azar Baradaran ◽  
Ali Valiani ◽  
Mustafa Ghanadian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Molecular Aspects

scholarly journals Cigarette Smoke Exposure Impairs β-Cell Function Through Activation of Oxidative Stress and Ceramide Accumulation

2019 ◽  
Author(s):  
Xin Tong ◽  
Zunaira Chaudry ◽  
Chih-Chun Lee ◽  
Robert N. Bone ◽  
Sukrati Kanojia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Smoking Cessation ◽  
Weight Gain ◽  
Cell Function ◽  
Ex Vivo ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Β Cell Function ◽  
Ceramide Accumulation

ABSTRACTObjectivesEpidemiological studies indicate that first- and second-hand cigarette smoke (CS) exposure are important risk factors for the development of type 2 diabetes (T2D). Additionally, elevated diabetes risk has been reported to occur within a short period of time after smoking cessation, and health risks associated with smoking are increased when combined with obesity. At present, the mechanisms underlying these associations remain incompletely understood. The objective of this study was to test the impact of CS exposure on pancreatic β-cell function using rodent and in vitro models.MethodsBeginning at 8 weeks of age, C57BL/6J mice were concurrently fed high fat-diet (HFD) and exposed to CS for 11 weeks, followed by an additional 11 weeks of smoking cessation with continued HFD exposure. Glucose tolerance testing was performed during CS exposure and during the cessation period. Cultured β-cells (INS-1) and primary islets were exposed ex vivo to CS extract (CSE), and β-cell function and viability were tested. Since CS increases ceramide in lungs cells and these bioactive sphingolipids have been implicated in pancreatic β-cell dysfunction in diabetes, islet and β-cell sphingolipid levels were measured in islets from CS-exposed mice and in CSE-treated islets and INS-1 cells using liquid chromatography-tandem mass spectrometry.ResultsCompared to HFD-fed ambient air-exposed mice, HFD-fed and CS- exposed mice had reduced weight gain and better glucose tolerance during the active smoking period. Following smoking cessation, CS-mice exhibited rapid weight gain and a significantly greater increase in glucose intolerance compared to non-smoking control mice. CS-exposed mice had higher serum proinsulin/insulin ratios, indicative of β-cell dysfunction, significantly lower β-cell mass (p=0.02), and reduced β-cell proliferation (p=0.006), and increased islet ceramide accumulation. Ex vivo exposure of isolated islets to CSE was sufficient to increase islet ceramide accumulation, reduce insulin gene expression and glucose-stimulated insulin secretion, and increase β-cell oxidative and ER stress. Treatment with the antioxidant N-acetylcysteine, markedly attenuated the effects of CSE on ceramide levels, restored β-cell function and survival, and increased cyclin D2 expression, while also reducing activation of β-cell ER and oxidative stress.ConclusionsOur results indicate that CS exposure inhibits insulin production, processing, and secretion and reduced β-cell viability and proliferation. These effects were linked to increased β-cell oxidative and ER stress and ceramide accumulation. Mice fed HFD continued to experience detrimental effects of CS exposure even during smoking cessation. Elucidation of mechanisms by which CS exposure impairs β-cell function in synergy with obesity will help design therapeutic and preventive interventions for both active and former smokers.

scholarly journals The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes

2021 ◽  
Vol 22 (4) ◽  
pp. 1509
Author(s):  
Natsuki Eguchi ◽  
Nosratola D. Vaziri ◽  
Donald C. Dafoe ◽  
Hirohito Ichii
Keyword(s):  
Oxidative Stress ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Antioxidative Capacity ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Levels ◽  
Cell Dysfunction ◽  
Elevated Glucose ◽  
Β Cell Function

Diabetes is a chronic metabolic disorder characterized by inappropriately elevated glucose levels as a result of impaired pancreatic β cell function and insulin resistance. Extensive studies have been conducted to elucidate the mechanism involved in the development of β cell failure and death under diabetic conditions such as hyperglycemia, hyperlipidemia, and inflammation. Of the plethora of proposed mechanisms, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and oxidative stress have been shown to play a central role in promoting β cell dysfunction. It has become more evident in recent years that these 3 factors are closely interrelated and importantly aggravate each other. Oxidative stress in particular is of great interest to β cell health and survival as it has been shown that β cells exhibit lower antioxidative capacity. Therefore, this review will focus on discussing factors that contribute to the development of oxidative stress in pancreatic β cells and explore the downstream effects of oxidative stress on β cell function and health. Furthermore, antioxidative capacity of β cells to counteract these effects will be discussed along with new approaches focused on preserving β cells under oxidative conditions.

Role of Oxidative Stress in Pancreatic β-Cell Dysfunction

2004 ◽  
Vol 1011 (1) ◽  
pp. 168-176 ◽  
Author(s):  
YOSHITAKA KAJIMOTO ◽  
HIDEAKI KANETO
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction

Long noncoding RNA OIP5-AS1 overexpression promotes viability and inhibits high glucose-induced oxidative stress of cardiomyocytes by targeting microRNA-34a/SIRT1 axis in diabetic cardiomyopathy

2020 ◽  
Vol 21 ◽  
Author(s):  
Haiyun Sun ◽  
Chong Wang ◽  
Ying Zhou ◽  
Xingbo Cheng
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Promoting Effect

Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes. This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1) on the viability and oxidative stress of cardiomyocyte in DCM. Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells. The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied to analyze the protein expression of SIRT1. Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated. The functional experiment stated that OIP5-AS1 overexpression increased the viability and SOD level, while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the promoting effect on viability, and mitigated the reduction effect on oxidative stress caused by OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells. Conclusions: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for DCM.

Sign in / Sign up

Export Citation Format

Share Document