scholarly journals High glucose inhibits glucose‐6‐phosphate dehydrogenase, leading to increased oxidative stress and β‐cell apoptosis

2009 ◽  
Vol 24 (5) ◽  
pp. 1497-1505 ◽  
Author(s):  
Zhaoyun Zhang ◽  
Chong Wee Liew ◽  
Diane E. Handy ◽  
Yingyi Zhang ◽  
Jane A. Leopold ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Β Cell ◽  
Glucose 6 Phosphate Dehydrogenase

scholarly journals CD36 regulates β cell differentiation and influences type 2 diabetic sepsis

2021 ◽  
Author(s):  
Huogen Liu ◽  
Ling Gu ◽  
Yundi Shi ◽  
Hailin Shu ◽  
Fengming Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Cell Clone ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Β Cell ◽  
Type 2 Diabetic

Abstract Background This study aimed to investigate the diagnostic function of CD36 in type 2 diabetic (T2DM) sepsis complications (T2DSC) and its effect on β-cell differentiation. Methods First, Age - and sex-matched T2DM patients, T2DSC patients and healthy people (50 cases each) were included. Quantitative polymerase chain reaction was used to measure CD36, FOXO1, PDX1, MAFA, insulin, SOX9, Neurog3 and NANOG expression in blood samples. Second, cultured human β-cell line EndoC-βH1 and the interference and overexpression of CD36. Cell clone, apoptosis, inflammatory cytokine, oxidative stress and β-cell differentiation related proteins were also analysed. Third, examined the role of CD36 in high glucose, LPS-induced β-cell. Results CD36 mRNA, and endocrine progenitor β-cell biomarkers SOX9, Neurog3 and NANOG were significantly increased in T2DM than control group, whereas the β-cell maturation biomarkers FOXO1, PDX1, MAFA and insulin were significantly decreased. Compared with the T2DM group, CD36 and FOXO1 were significantly increased in T2DSC, but PDX1, insulin, MAFA, SOX9, Neurog3 and NANOG were significantly decreased. The receiver operating characteristic curve revealed that CD36 was useful for distinguishing T2MD and T2DSC from the control group. Furthermore, CD36 overexpression increased β-cell apoptosis and the secretion of IL-1β, IL-8 TNF-α, malondialdehyde and reactive oxygen species. CD36 induced cell defferentiation. Lastly, CD36 knockdown could inhibit the high glucose and LPS-induced cell apoptosis, inflammatory, oxidative stress and cell defferentiation. Conclusion Significant increase in CD36 can be used as a biomarker for T2MD and T2DSC. CD36 promotes T2MD or T2DSC development by inducing β-cell inflammatory and oxidative stress and defferentiation.

scholarly journals Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity

2014 ◽  
Vol 224 (3) ◽  
pp. 215-224 ◽  
Author(s):  
Suwattanee Kooptiwut ◽  
Wanthanee Hanchang ◽  
Namoiy Semprasert ◽  
Mutita Junking ◽  
Thawornchai Limjindaporn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Ang Ii ◽  
Pancreatic Β Cell ◽  
Glucose Medium ◽  
Β Cell ◽  
High Glucose Medium ◽  
Cells Cultured

Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin–angiotensin–aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47phox mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47phox mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47phox. In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.

scholarly journals Superoxide Destabilization of β-Catenin Augments Apoptosis of High-Glucose-Stressed Mesangial Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2934-2942 ◽  
Author(s):  
Chun-Liang Lin ◽  
Jeng-Yi Wang ◽  
Jih-Yang Ko ◽  
Kameswaran Surendran ◽  
Yu-Ting Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Renal Tissue ◽  
Dominant Negative ◽  
Gsk 3Β

Intense mesangial cell apoptosis contributes to the pathogenesis of diabetic nephropathy. Although reactive oxygen radicals and Wnt signaling components are potent regulators that modulate renal tissue remodeling and morphogenesis, cross-talk between oxidative stress and Wnt/β-catenin signaling in controlling high-glucose-impaired mesangial cell survival and renal function have not been tested. In this study, high glucose induced Ras and Rac1 activation, superoxide burst, and Wnt5a/β-catenin destabilization and subsequently promoted caspase-3 and poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures. The pharmacological and genetic suppression of superoxide synthesis by superoxide dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant-negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK-3β) activation and caspase-3 and poly (ADP-ribose) polymerase degradation. Inactivation of Ras and Racl also reversed Wnt/β-catenin expression and survival of mesangial cells. Stabilization of β-catenin by the transfection of stable β-catenin (Δ45) and kinase-inactive GSK-3β attenuated high-glucose-mediated mesangial cell apoptosis. Exogenous superoxide dismutase administration attenuated urinary protein secretion in diabetic rats and abrogated diabetes-mediated reactive oxygen radical synthesis in renal glomeruli. Immunohistological observation revealed that superoxide dismutase treatment abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and increased Wnt5a/β-catenin expression in renal glomeruli. Taken together, high glucose induced oxidative stress and apoptosis in mesangial cells. The Ras and Rac1 regulation of superoxide appeared to raise apoptotic activity by activating GSK-3β and inhibiting Wnt5a/β-catenin signaling. Controlling oxidative stress and Wnt/β-catenin signaling has potential for protecting renal tissue against the deleterious effect of high glucose.

Downregulation of General Control Nonderepressible 2/Eukaryotic Initiation Factor 2α Attenuates Inflammation, Oxidative Stress and Cell Apoptosis in Retinal Cells Induced by High Glucose

2021 ◽  
Vol 11 (8) ◽  
pp. 1497-1505
Author(s):  
Shuyu Zhao ◽  
Yuqian Yin ◽  
Hong Qin
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Western Blot ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Colorimetric Method ◽  
Underlying Mechanism ◽  
Initiation Factor ◽  
Western Blot Assay ◽  
And Oxidative Stress

Background: Diabetic retinopathy (DR), the frequent complication of diabetes mellitus, has been the main factor of clinical blindness. It is of great clinical significance to seek a novel therapeutic target of DR. The present study aims to investigate the important role of GCN2/eIF2α in DR and the underlying mechanism. Materials and Methods: The expression levels of GCN2 and p-eIF2α were measured by western blot assay and q-PCR. The inflammation levels were assessed by ELISA assay and oxidative stress was measured by colorimetric method. Then, the key proteins related to the function of endothelial cell were measured by western blot assay. Cell apoptotic rate was detected by flow cytometry and proteins related to cell apoptosis were detected by western blot assay. Results: High glucose activated GCN2/eIF2α signaling pathway in HRCECs. Downregulation of GCN2 attenuated HG-induced cell apoptosis, inflammatory and oxidative stress in HRCECs. Meanwhile, downregulation of GCN2 ameliorated HG-induced endothelial cell dysfunction. Inhibition of GCN2 inhibited p-eIF2α, ATF4, CHOP and activated UCP2. Conclusion: The results in this study proved that knockdown of GCN2 could significantly mitigate HG-induced injury, suggesting GCN2/eIF2α as a potential target for DR therapy.

Lack of TXNIP protects β-cells against glucotoxicity

2008 ◽  
Vol 36 (5) ◽  
pp. 963-965 ◽  
Author(s):  
Anath Shalev
Keyword(s):  
Cell Death ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Causative Role ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Levels ◽  
Primary Mouse ◽  
Diabetes Progression

Glucotoxicity plays a major role in pancreatic β-cell apoptosis and diabetes progression, but the factors involved have remained largely unknown. Our recent studies have identified TXNIP (thioredoxin-interacting protein) as a novel pro-apoptotic β-cell factor that is induced by glucose, suggesting that TXNIP may play a role in β-cell glucotoxicity. Incubation of INS-1 β-cells and isolated primary mouse and human islets at high glucose levels led to a significant increase in TXNIP as well as in apoptosis. Very similar results were obtained in vivo in islets of diabetic mice. To determine whether TXNIP plays a causative role in glucotoxic β-cell death, we used TXNIP-deficient islets of HcB-19 mice harbouring a natural nonsense mutation in the TXNIP gene. We incubated islets of HcB-19 and C3H control mice at low and high glucose levels and assessed them for TXNIP expression and apoptosis. Interestingly, whereas in C3H islets, high glucose levels led again to significant elevation of TXNIP and apoptosis levels as measured by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) and cleaved caspase 3, no increase in apoptosis was observed in TXNIP-deficient HcB-19 islets, indicating that TXNIP is required for β-cell death caused by glucotoxicity. Thus inhibition of TXNIP protects against glucotoxic β-cell apoptosis and therefore may represent a novel therapeutic approach to halt diabetes progression.

scholarly journals Cholesterol induces pancreatic β cell apoptosis through oxidative stress pathway

2011 ◽  
Vol 16 (5) ◽  
pp. 539-548 ◽  
Author(s):  
Xiuli Lu ◽  
Jianli Liu ◽  
Fangfang Hou ◽  
Zhenqing Liu ◽  
Xiangyu Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Oxidative Stress Pathway ◽  
Stress Pathway

Sequoyitol Alleviates High Glucose-Induced Inflammation, Oxidative Stress and Apoptosis of Retina Epithelial Cells

2021 ◽  
Vol 11 (5) ◽  
pp. 1003-1009
Author(s):  
Liping Hu ◽  
Rui Zhang ◽  
Jianhua Wu ◽  
Chao Feng ◽  
Li Kong
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Therapeutic Potential ◽  
Promoting Effect ◽  
Related Factors ◽  
And Oxidative Stress

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes, contributing to visual impairment and blindness. Sequoyitol (Seq), a form of inositol derivatives, has been demonstrated to be a therapeutic potential for diabetes and diabetic nephropathy. The aim of this study is to explore the effects of Seq on DR. ARPE-19 cells were cultured in high glucose (HG) condition to simulate DR in vitro. Seq (1,10 and 20 µM) was applied for treatment. CCK-8 assay was performed to detect cell viability. Flow cytometry analysis was conducted to determine cell apoptosis rate. The production level of inflammatory cytokines and oxidative stress-related factors were determined using their commercial kits. The protein expressions of corresponding genes were detected using western blotting. The results revealed that Seq significantly increased cell viability and protein expression of PCNA and Ki67 which were decreased after HG induction. HG promoted cell apoptosis by decreasing protein expression of Bcl-2 and increasing protein expression of Bax and cleaved caspase-3, which was then reversed by Seq treatment. Besides, Seq abolished the promoting effects of HG on the production of pro-inflammatory cytokines and oxidative stress-related factors. Furthermore, Seq suppressed the promoting effect of HG on the activation of NF-κB signaling by inhibiting phosphorylation of kBa and NF-κB nucleus translocation. These results indicated that Seq might protect ARPE-19 cells against HG-induced cell viability, apoptosis, inflammation and oxidative stress by regulating NF-κB signaling, providing evidence for the potential application of Seq in the therapy of DR.

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