17β-Estradiol/extrogen receptor β alleviates apoptosis and enhances matrix biosynthesis of nucleus pulposus cells through regulating oxidative damage under a high glucose condition

2018 ◽  
Vol 107 ◽  
pp. 1004-1009 ◽  
Author(s):  
Di Yang ◽  
Danjie Zhu ◽  
Shaoyu Zhu ◽  
Fabo Feng ◽  
Chen Gong ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Nucleus Pulposus ◽  
High Glucose ◽  
Nucleus Pulposus Cells ◽  
High Glucose Condition ◽  
17Β Estradiol ◽  
Glucose Condition

scholarly journals High Glucose Induces Autophagy through PPARγ-Dependent Pathway in Human Nucleus Pulposus Cells

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chang Jiang ◽  
Shuhao Liu ◽  
Yuanwu Cao ◽  
Hongping Shan
Keyword(s):  
Nucleus Pulposus ◽  
High Glucose ◽  
Beclin 1 ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Nucleus Pulposus Cells ◽  
Connective Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
High Glucose Condition ◽  
Dependent Pathway

Diabetes mellitus is a multiorgan disorder affecting many types of connective tissues, including bone and cartilage. High glucose could accelerate the autophagy in nucleus pulposus (NP) cells. In our present study, we investigated whether peroxisome proliferator-activated receptor γ (PPAR-γ) pathway is involved into autophagy regulation in NP cells under high glucose condition. After NP cells were treated with different high glucose concentrations for 72 hours, the rate of autophagy increased. Moreover, the levels of PPARγ, Beclin-1, and LC3II were significantly increased and p62 was significantly decreased compared to control group. Then, NP cells were treated with high glucose plus PPARγ agonist or PPARγ antagonist, respectively. The rate of autophagy and the levels of Beclin-1 and LC3II increased, but p62 decreased when PPARγ agonist was used. On the contrary, the rate of autophagy and the levels of Beclin-1 and LC3II decreased, while p62 increased when PPARγ antagonist was added. These results suggested that autophagy induced by high glucose in NP cells was through PPARγ-dependent pathway.

Effect of metformin and celecoxib on cytotoxicity and release of GDF-15 from human mesenchymal stem cells in high glucose condition

2017 ◽  
Vol 35 (7) ◽  
pp. 407-413 ◽  
Author(s):  
Elaheh Zafarvahedian ◽  
Azam Roohi ◽  
Mohammad Reza Sepand ◽  
Seyed Nasser Ostad ◽  
Mohammad Hossein Ghahremani
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Human Mesenchymal Stem Cells ◽  
High Glucose Condition ◽  
Glucose Condition

scholarly journals PPARβ/δ accelerates bone regeneration in diabetic mellitus by enhancing AMPK/mTOR pathway-mediated autophagy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miao Chen ◽  
Dian Jing ◽  
Rui Ye ◽  
Jianru Yi ◽  
Zhihe Zhao
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Bone Healing ◽  
High Glucose ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Regulatory Effect ◽  
Compound C ◽  
High Glucose Condition ◽  
Glucose Condition

Abstract Background Diabetic patients are more vulnerable to skeletal complications. Peroxisome proliferators-activated receptor (PPAR) β/δ has a positive regulatory effect on bone turnover under physiologic glucose concentration; however, the regulatory effect in diabetes mellitus has not been investigated yet. Herein, we explored the effects of PPARβ/δ agonist on the regeneration of diabetic bone defects and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) under a pathological high-glucose condition. Methods We detected the effect of PPARβ/δ agonist on osteogenic differentiation of rBMSCs in vitro and investigated the bone healing process in diabetic rats after PPARβ/δ agonist treatment in vivo. RNA sequencing was performed to detect the differentially expressed genes and enriched pathways. Western blot was performed to detect the autophagy-related protein level. Laser confocal microscope (LSCM) and transmission electron microscope (TEM) were used to observe the formation of autophagosomes. Results Our results demonstrated that the activation of PPARβ/δ can improve the osteogenic differentiation of rBMSCs in high-glucose condition and promote the bone regeneration of calvarial defects in diabetic rats, while the inhibition of PPARβ/δ alleviated the osteogenic differentiation of rBMSCs. Mechanistically, the activation of PPARβ/δ up-regulates AMPK phosphorylation, yielding mTOR suppression and resulting in enhanced autophagy activity, which further promotes the osteogenic differentiation of rBMSCs in high-glucose condition. The addition of AMPK inhibitor Compound C or autophagy inhibitor 3-MA inhibited the osteogenesis of rBMSCs in high-glucose condition, suggesting that PPARβ/δ agonist promotes osteogenic differentiation of rBMSCs through AMPK/mTOR-regulated autophagy. Conclusion In conclusion, our study demonstrates the potential role of PPARβ/δ as a molecular target for the treatment of impaired bone quality and delayed bone healing in diabetic patients for the first time.

ERM Complex, a Therapeutic Target for Vascular Leakage Induced by Diabetes

2021 ◽  
Vol 28 ◽  
Author(s):  
Olga Simó-Servat ◽  
Hugo Ramos ◽  
Patricia Bogdanov ◽  
Marta García-Ramírez ◽  
Jordi Huerta ◽  
...  
Keyword(s):  
High Glucose ◽  
Therapeutic Target ◽  
Vascular Leakage ◽  
Cell Permeability ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Erm Proteins ◽  
High Glucose Condition ◽  
Tnf Α ◽  
Glucose Condition

Background: Ezrin, radixin, and moesin (the ERM complex) interact directly with membrane proteins regulating their attachment to actin filaments. ERM protein activation modifies cytoskeleton organization and alters the endothelial barrier function, thus favoring vascular leakage. However, little is known regarding the role of ERM proteins in diabetic retinopathy (DR). Objective: This study aimed to examine whether overexpression of the ERM complex exists in db/db mice and its main regulating factors. Methods: 9 male db/db mice and 9 male db/+ aged 14 weeks were analyzed. ERM proteins were assessed by western blot and by immunohistochemistry. Vascular leakage was determined by the Evans blue method. To assess ERM regulation, HRECs were cultured in a medium containing 5.5 mM D-glucose (mimicking physiological conditions) and 25 mM D-glucose (mimicking hyperglycemia that occurs in diabetic patients). Moreover, treatment with TNF-α, IL-1β, or VEGF was added to a high glucose condition. The expression of ERM proteins was quantified by RT-PCR. Cell permeability was evaluated by measuring movements of FITC-dextran. Results: A significant increase of ERM in diabetic mice in comparison with non-diabetic mice was observed. A high glucose condition alone did not have any effect on ERM expression. However, TNF-α and IL-1β induced a significant increase in ERM proteins. Conclusion: The increase of ERM proteins induced by diabetes could be one of the mechanisms involved in vascular leakage and could be considered as a therapeutic target. Moreover, the upregulation of the ERM complex by diabetes is induced by inflammatory mediators rather than by high glucose itself.

scholarly journals Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by high glucose through PI3K/Akt/caspase-3 signaling pathway

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Yao Ming-yan ◽  
Zhang Jing ◽  
Guo Shu-qin ◽  
Bai Xiao-liang ◽  
Li Zhi-hong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
High Glucose ◽  
Caspase 3 ◽  
Maximum Effect ◽  
Ros Generation ◽  
Protective Effects ◽  
Small Interfering Rnas ◽  
Nucleus Pulposus Cells ◽  
Pi3k Inhibitor Ly294002

Abstract Diabetes mellitus (DM) is a potential etiology of disc degeneration. Glucagon-like peptide-1 (GLP-1) is currently regarded as a powerful treatment option for type 2 diabetes. Apart from the beneficial effects on glycaemic control, GLP-1 has been reported to exert functions in a variety of tissues on modulation of cell proliferation, differentiation, and apoptosis. However, little is known regarding the effects of GLP-1 on nucleus pulposus cells (NPCs). In the present study, we investigated the effects of liraglutide (LIR), a long-lasting GLP-1 analogue, on apoptosis of human NPCs and the underlying mechanisms involved. We confirmed the presence of GLP-1 receptor (GLP-1R) in NPCs. Our data demonstrated that liraglutide inhibited the apoptosis of NPCs induced by high glucose (HG), as detected by Annexin V/Propidium Iodide (PI) and ELISA assays. Moreover, liraglutide down-regulated caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further analysis suggested that liraglutide suppressed reactive oxygen species (ROS) generation and stimulated the phosphorylation of Akt under HG condition. Pretreatment of cells with the Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY) and small interfering RNAs (siRNAs) GLP-1R abrogated the liraglutide-induced activation of Akt and the protective effects on NPCs’ apoptosis. In conclusion, liraglutide could directly protect NPCs against HG-induced apoptosis by inhibiting oxidative stress and activate the PI3K/Akt/caspase-3 signaling pathway via GLP-1R.

The Effect of High-Glucose Condition on Insulin Binding to IM-9 Lymphocytes

1987 ◽  
Vol 19 (07) ◽  
pp. 316-318 ◽  
Author(s):  
N. Watanabe ◽  
M. Kobayashi ◽  
M. Iwasaki ◽  
O. Ishibashi ◽  
Y. Takata ◽  
...  
Keyword(s):  
High Glucose ◽  
Insulin Binding ◽  
High Glucose Condition ◽  
Glucose Condition
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