scholarly journals LncRNA LEGLTBC Functions as a ceRNA to Antagonize the Effects of miR-34a on the Downregulation of SIRT1 in Glucolipotoxicity-Induced INS-1 Beta Cell Oxidative Stress and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Xiang Kong ◽  
Chong-xiao Liu ◽  
Guo-dong Wang ◽  
Hui Yang ◽  
Xin-ming Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Injury ◽  
Cell Damage ◽  
High Serum ◽  
Cell Dysfunction ◽  
Beta Cell Damage

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose and/or high serum free fatty acids. Chronic hyperlipidemia causes the dysfunction of pancreatic beta cells, which is aggravated in the presence of hyperglycemia (glucolipotoxicity). Long noncoding RNAs (lncRNAs) have been suggested to play key roles in type 1 diabetes mellitus development. However, their roles in glucolipotoxicity-induced beta cell dysfunction are not fully understood. In the present study, we identified the differentially expressed lncRNAs in INS-1 cells exposed to high glucose and palmitate (HG/PA). Among the dysregulated lncRNAs, NONRATT003679.2 (low expression in glucolipotoxicity-treated beta cells (LEGLTBC)) was involved in glucolipotoxicity-evoked rat islet beta cell damage. LEGLTBC functioned as a molecular sponge of miR-34a in INS-1 cells. Additionally, SIRT1 was identified as a target of miR-34a and LEGLTBC promoted SIRT1 expression by sponging miR-34a. The upregulation of LEGLTBC attenuated HG/PA-induced INS-1 cell injury through the promotion of SIRT1-mediated suppression of ROS accumulation and apoptosis. This is the first study to comprehensively identify the lncRNA expression profiling of HG/PA-treated INS-1 beta cells and to demonstrate that LEGLTBC functions as a competing endogenous RNA and regulates miR-34a/SIRT1-mediated oxidative stress and apoptosis in INS-1 cells undergoing glucolipotoxicity.

scholarly journals Prevention of Oxidative Stress-Induced Pancreatic Beta Cell Damage by Broussonetia kazinoki Siebold Fruit Extract via the ERK-Nox4 Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 406 ◽  
Author(s):  
Hyo-Jin Kim ◽  
Donghee Kim ◽  
Haelim Yoon ◽  
Cheol Soo Choi ◽  
Yoon Sin Oh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Damage ◽  
Beta Cell Death ◽  
Min6 Cells ◽  
Erk Phosphorylation ◽  
Beta Cell Damage

Pancreatic beta cells are vulnerable to oxidative stress, which causes beta cell death and dysfunction in diabetes mellitus. Broussonetia kazinoki Siebold (BK) is a widely used herbal medicine, but its potential effects against beta cell death-induced diabetes have not been studied. Therefore, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against streptozotocin (STZ)-induced toxicity in pancreatic beta cells. Intraperitoneal injection of STZ in mice induced hyperglycemia; however, oral administration of BKFE significantly decreased the blood glucose level as well as HbA1c levels. BKFE treatment improved glucose tolerance and increased body weight in diabetic mice. Moreover, BKFE treatment resulted in increased serum insulin levels and insulin expression in the pancreas as well as decreased 4-hydroxynonenal levels induced by oxidative stress. Treatment with STZ decreased cell viability of mouse insulinoma cells (MIN6), which was blocked by BKFE pretreatment. BKFE significantly inhibited apoptotic cells and decreased the expression levels of cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase (PARP) induced by STZ treatment. Production of reactive oxygen species in STZ-treated MIN6 cells was also significantly decreased by treatment with BKFE. Erk phosphorylation and Nox4 levels increased in STZ-treated MIN6 cells and the pancreas of mice injected with STZ and this increase was inhibited by treatment with BKFE. Inhibition of Erk phosphorylation by treatment with the PD98059 inhibitor or siRNA Erk also blocked the expression of Nox4 induced by STZ treatment. In conclusion, BKFE inhibits Erk phosphorylation, which in turn prevents STZ-induced oxidative stress and beta cell apoptosis. These results suggested that BKFE can be used to prevent or treat beta cell damage in diabetes.

scholarly journals Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 658 ◽  
Author(s):  
Ming-Shih Lee ◽  
Charng-Cherng Chyau ◽  
Chi-Ping Wang ◽  
Ting-Hsuan Wang ◽  
Jing-Hsien Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Injury ◽  
Pancreatic Beta Cell ◽  
B Cell Lymphoma ◽  
Pancreatic Cell ◽  
Traditional Chinese Herbal Medicine ◽  
Lotus Seedpod

Oxidative stress is highly associated with the development of diabetes mellitus (DM), especially pancreatic beta-cell injury. Flavonoids derived from plants have caused important attention in the prevention or treatment of DM. Lotus seedpod belongs to a traditional Chinese herbal medicine and has been indicated to possess antioxidant, anti-age, anti-glycative, and hepatoprotective activities. The purpose of this study was to demonstrate the pancreatic beta-cell protective effects of lotus seedpod aqueous extracts (LSE) against oxidative injury. According to HPLC/ESI-MS-MS method, LSE was confirmed to have flavonoids derivatives, especially quercetin-3-glucuronide (Q3G). In vitro, LSE dose-dependently improved the survival and function of rat pancreatic beta-cells (RIN-m5F) from hydrogen peroxide (H2O2)-mediated loss of cell viability, impairment of insulin secretion, and promotion of oxidative stress. LSE showed potential in decreasing the H2O2-induced occurrence of apoptosis. In addition, H2O2-triggered acidic vesicular organelle formation and microtubule-associated protein light chain 3 (LC3)-II upregulation, markers of autophagy, were increased by LSE. Molecular data explored that antiapoptotic and autophagic effects of LSE, comparable to that of Q3G, might receptively be mediated via phospho-Bcl-2-associated death promoter (p-Bad)/B-cell lymphoma 2 (Bcl-2) and class III phosphatidylinositol-3 kinase (PI3K)/LC3-II signal pathway. In vivo, LSE improved the DM symptoms and pancreatic cell injury better than metformin, a drug that is routinely prescribed to treat DM. These data implied that LSE induces the autophagic signaling, leading to protect beta-cells from oxidative stress-related apoptosis and injury.

scholarly journals Abnormal cannabidiol ameliorates inflammation preserving pancreatic beta cells in mouse models of experimental type 1 diabetes and beta cell damage

2021 ◽  
pp. 112361
Author(s):  
Isabel González-Mariscal ◽  
Macarena Pozo Morales ◽  
Silvana Y. Romero-Zerbo ◽  
Vanesa Espinosa-Jimenez ◽  
Alejandro Escamilla-Sánchez ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Mouse Models ◽  
Pancreatic Beta Cells ◽  
Cell Damage ◽  
Experimental Type ◽  
Beta Cell Damage

Cerium and Yttrium Oxide Nanoparticles and Nano-selenium Produce Protective Effects Against H2O2-induced Oxidative Stress in Pancreatic Beta Cells by Modulating Mitochondrial Dysfunction

2020 ◽  
Vol 8 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Shima Tavoosi ◽  
Amir Hossein Baghsheikhi ◽  
Seyed Vahid Shetab-Boushehri ◽  
Mona Navaei-Nigjeh ◽  
Nazanin Namazi Sarvestani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Beta Cell ◽  
Mitochondrial Dysfunction ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucagon Secretion ◽  
Oxide Nanoparticles ◽  
Beta Cell Line ◽  
Yttrium Oxide Nanoparticles

Background: Type 1 diabetes mellitus is characterized by the destruction of insulin- producing Beta cells in the pancreas. Researchers hope that islet transplantation will help to patients with insulin-dependent diabetes mellitus (IDDM). Oxidative stress is the most important challenge that beta cells face to it after isolation, and mitochondrial dysfunction is a crucial mediator in beta cells death. Hence, therapeutic approaches can shift to antioxidants through the application of nanoparticles such as cerium and yttrium oxide nanoparticles (Cer and Ytt Ox NPs) and nano-selenium (Nan Se). Objectives: This study evaluates the effects of Cer and Ytt Ox NPs and Nan Se on H2O2- induced oxidative stress in pancreatic beta cells with focus on mitochondrial dysfunction pathway. Methods: CRI-D2 beta-cell line were pretreated with Cer Ox NPs (200 µM) + Ytt Ox NPs (0.5 µg/mL) for 3 days and/or Nan Se (0.01 µM) for 1 day. Then markers of oxidative stress, mitochondrial dysfunction, insulin and glucagon secretion were measured. Results: We reported a decrease in H2O2-induced reactive oxygen species (ROS) level and glucagon secretion, and an increase in H2O2-reduced ATP/ADP ratio, MMP, as well as UCP2 protein expression, and insulin secretion by pretreatment of CRI-D2 cells with Cer and Ytt Ox NPs and/or Nan Se. Conclusion: We found maximum protective effect with Cer and Ytt Ox NPs on CRI-D2 beta-cell line exposed by H2O2 for keeping beta cells alive until transplant whereas combination of Cer and Ytt Ox NPs and Nan Se had very little protective effect in this condition.

scholarly journals Update on the Protective Molecular Pathways Improving Pancreatic Beta-Cell Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
François Mach ◽  
Franco Dallegri ◽  
Giorgio Luciano Viviani ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Molecular Pathways ◽  
Cell Dysfunction

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.

scholarly journals Beta Cell Autophagy in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Author(s):  
Charanya Muralidharan ◽  
Amelia K Linnemann
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Potential Role ◽  
Cell Dysfunction ◽  
Unconventional Secretion ◽  
Insulin Dependent

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic beta cells are destroyed resulting in hyperglycemia. This multi-factorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the beta cells may promote a change in the local immune mileu, contributing to autoimmunity. Therefore, many studies have been focused on intrinsic beta cell mechanisms that aid in restoration of cellular homeostasis under environmental conditions that cause dysfunction. One of these intrinsic mechanisms to promote homeostasis is autophagy, defects in which are clearly linked with beta cell dysfunction in the context of type 2 diabetes. Recent studies have now also pointed towards beta cell autophagy defects in the context of type 1 diabetes. In this perspectives review, we will discuss the evidence supporting a role for beta cell autophagy in the pathogenesis of type 1 diabetes, including a potential role for unconventional secretion of autophagosomes/lysosomes in the changing dialogue between the beta cell and immune cells.

Stable overexpression of p8 increases survival of INS-1E beta cells in response to streptozotocin (STZ)-induced beta cell damage in vitro

2009 ◽  
Vol 4 (S 01) ◽  
Author(s):  
G Päth ◽  
E Tsaroucha ◽  
N Perakakis ◽  
I Pilz ◽  
M Alt ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Cell Damage ◽  
Beta Cell Damage

scholarly journals Psoralea corylifoliaL. Seed Extract Ameliorates Streptozotocin-Induced Diabetes in Mice by Inhibition of Oxidative Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Eunhui Seo ◽  
Eun-Kyu Lee ◽  
Cheol Soon Lee ◽  
Kwang-Hoon Chun ◽  
Mi-Young Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Beta Cell ◽  
Cell Damage ◽  
Serum Insulin ◽  
Pancreatic Beta Cell ◽  
Beta Cell Death ◽  
Streptozotocin Induced Diabetes ◽  
Induced Apoptosis ◽  
Beta Cell Damage

Pancreatic beta-cell death is known to be the cause of deficient insulin production in diabetes mellitus. Oxidative stress is one of the major causes of beta-cell death. In this study, we investigated the effects ofPsoralea corylifoliaL. seed (PCS) extract on beta-cell death. Oral administration of PCS extract resulted in a significant improvement of hyperglycemia in streptozotocin-induced diabetic mice. PCS extract treatment improved glucose tolerance and increased serum insulin levels. To study the mechanisms involved, we investigated the effects of PCS extract on H2O2-induced apoptosis in INS-1 cells. Treatment with PCS extract inhibited cell death. PCS extract treatment decreased reactive oxygen species level and activated antioxidative enzymes. Among the major components of PCS extract, psoralen and isopsoralen (coumarins), but not bakuchiol, showed preventive effects against H2O2-induced beta-cell death. These findings indicate that PCS extract may be a potential pharmacological agent to protect against pancreatic beta-cell damage caused by oxidative stress associated with diabetes.

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