scholarly journals High glucose enhances CD39 expression in vascular endothelial cells

2014 ◽  
Vol 8 (2) ◽  
pp. 283-287
Author(s):  
Sudawadee Kongkhum ◽  
Mudtika Fungkrajai ◽  
Sompoch Prajan ◽  
Narisa Kengtrong Bordeerat ◽  
Kanyanath Piumngam ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Glucose ◽  
Cell Viability ◽  
High Glucose ◽  
Inflammatory Process ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels

Abstract Background: Diabetes mellitus (DM) patients lose their ability to control normal blood glucose levels, resulting in high blood glucose levels (hyperglycemia). Hyperglycemia causes DM complications. This involves responses of vascular endothelial cells (VECs) to hyperglycemia, affecting inflammatory process and platelet activity. Ecto-enzyme CD39 is expressed on VECs, catalyzing the hydrolysis of ATP and ADP to AMP and, consequently, regulating inflammatory process and platelet activation. Objective: We studied whether high glucose concentration has an effect on CD39 expression on VECs. Methods: Cultured human umbilical vein endothelial cells (HUVEC) were used as a model of study. HUVEC were cultured in different glucose conditions (4, 9, 24, and 34 mM) for 24 hours. Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based assay and expression of CD39 was examined by using SDS-PAGE and western blot techniques. Results: HUVEC were cultured in normal (4 and 9 mM) or high (24 and 34 mM) glucose concentrations for short term (24 hours). The results showed that high glucose (24 and 34 mM) reduced cell viability to 89.5 ± 11.3 and 86.3 ± 13.5 (mean ± SD), compared with control (4 mM), respectively. High glucose also induced increases in CD39 expression in HUVEC. Conclusion: High glucose decreases cell viability and increases CD39 expression in HUVEC, suggesting involvement of CD39 in cell responses to high glucose.

scholarly journals Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

2018 ◽  
Vol 45 (2) ◽  
pp. 558-571 ◽  
Author(s):  
Yun Yi ◽  
Yulin Shen ◽  
Qin Wu ◽  
Jingan Rao ◽  
Shu Guan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Western Blotting ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Control Group ◽  
Vascular Endothelial ◽  
A2b Receptor ◽  
High Glucose Group ◽  
Glucose Group

Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucose-induced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A2B siRNA. The expression of the adenosine A2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2.

scholarly journals RNA sequencing reveals BMP4 as a basis for the dual-target treatment of diabetic retinopathy

2020 ◽  
Author(s):  
Lijie Dong ◽  
Zhe Zhang ◽  
Xun Liu ◽  
Qiong Wang ◽  
Yaru Hong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Anti Vegf ◽  
Target Treatment ◽  
Dual Target

Abstract Backgroud: Diabetic retinopathy, currently considered a neurovascular disease, has become the major cause of blindness. Continuously high glucose levels are regarded as a risk factor for DR. Intravitreal injection of anti-VEGF drugs is a classic treatment for DR; however, anti-VEGF drugs can exacerbate fibrosis and eventually lead to retinal detachment.Methods: We explored changes in gene expression in high-glucose-induced vascular endothelial cells using RNA sequencing technology, utilized transcriptome signatures to explore the pathogenesis of DR and identified new treatments that can provide dual-target intervention for angiogenesis and fibrosis. We identified BMP4 and SMAD9 among 449 differentially expressed genes from RNA-seq data and investigated the expression of these two genes in the blood of diabetes patients and in STZ-induced rat retinas. Moreover, considering that DR is a multifactorial and multicellular disease, we used H2O2, AGEs, CoCl2, 4HNE and hypoxia to induce three human retinal cell types (Müller, RPE and HRCECs) to simulate the pathogenesis of DR and then verified the overexpression of these two genes in the cell models. We further tested the effects of BMP4 on retinal cells. Results: The results demonstrated that BMP4 and SMAD9 were highly expressed in both in vivo and in vitro models, while BMP4 could significantly upregulate the expression of SMAD9 and promote the expression of VEGF and fibrosis factors.Conclusions: This study is the first to analyze the mechanism by which high glucose levels affect retinal vascular endothelial cells through RNA transcriptome sequencing and indicates that BMP4 may be a potential target for the dual-target treatment (anti-VEGF and antifibrosis) of DR.

High Blood Glucose Levels Affect Auditory Brainstem Responses after Acoustic Overexposure in Rats

2021 ◽  
pp. 1-8
Author(s):  
Jae-Hun Lee ◽  
Sang Hee Ji ◽  
Jae Yun Jung ◽  
Min Young Lee ◽  
Chi-Kyou Lee
Keyword(s):  
Blood Glucose ◽  
Hearing Threshold ◽  
Auditory Brainstem ◽  
Diabetic Rats ◽  
Control Groups ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hearing Function ◽  
Brainstem Response

Introduction: Diabetes mellitus (DM) is a systemic disease characterized by hyperglycemia and several pathological changes. DM-related hearing dysfunctions are associated with histological changes. Here, we explore hearing function and synaptic changes in the inner hair cells (IHCs) of rats with streptozotocin (STZ)-induced diabetes. Methods: STZ was injected to trigger diabetes. Rats with DM were exposed to narrow-band noise (105 dB SPL) for 2 h, and hearing function was analyzed 1, 3, 7, and 14 days later. Both the hearing threshold and the peak 1 amplitude of the tone auditory brainstem response were assessed. After the last functional test, animals were sacrificed for histological evaluation. Results: We found no changes in the baseline hearing threshold; however, the peak 1 amplitude at the low frequency (4 kHz) was significantly higher in both DM groups than in the control groups. The hearing threshold had not fully recovered at 14 days after diabetic rats were exposed to noise. The peak 1 amplitude at the higher frequencies (16 and 32 kHz) was significantly larger in both DM groups than in the control groups. The histological analysis revealed that the long-term DM group had significantly more synapses in the 16 kHz region than the other groups. Conclusions: We found that high blood glucose levels increased peak 1 amplitudes without changing the hearing threshold. Diabetic rats were less resilient in threshold changes and were less vulnerable to peak 1 amplitude and synaptic damage than control animals.

Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy

2021 ◽  
Vol 271 ◽  
pp. 113855
Author(s):  
Junxiao Xi ◽  
Yuezhao Rong ◽  
Zifeng Zhao ◽  
Yihai Huang ◽  
Pu Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial

Influence of glucose levels on clinical outcome after mechanical thrombectomy for large-vessel occlusion: a systematic review and meta-analysis

2021 ◽  
pp. neurintsurg-2021-017771
Author(s):  
Carlos Perez-Vega ◽  
Ricardo A Domingo ◽  
Shashwat Tripathi ◽  
Andres Ramos-Fresnedo ◽  
Samir Kashyap ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Clinical Outcome ◽  
Mechanical Thrombectomy ◽  
Meta Analysis ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.

Sitagliptin: A DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

2011 ◽  
Vol 3 ◽  
pp. CMT.S6227 ◽  
Author(s):  
Kathryn MS Johnson ◽  
Kathleen Schurr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetes Therapy ◽  
High Blood Glucose ◽  
Adverse Side Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) has become an epidemic, with worldwide projections indicating that more than 336 million people will be afflicted with the disease by 2030. T2DM is characterized by inappropriately high blood glucose levels due to a deficiency in insulin secretion, action, or both. Despite the horrific complications that occur with chronic elevations of blood glucose levels, less than half of those with T2DM do not maintain proper glycemic control. Sitagliptin (Januvia, Merck and Co., Whitehouse Station, New Jersey) is a novel diabetes therapy approved for use in the U.S. and Europe. This small molecule inhibits the activity of DPP-4, a peptidase that degrades the glucoregulatory hormone GLP-1. Sitagliptin increases glucoregulation in individuals with T2DM both as a monotherapy and in combination with other antihyperglycemic drugs, with a low risk of adverse side effects.

Sign in / Sign up

Export Citation Format

Share Document