Cell‐specific insulin resistance: implications for atherosclerosis

Rajwani, Adil; Cubbon, Richard M; Wheatcroft, Stephen

doi:10.1002/dmrr.2336

Cited by 18 publications

(13 citation statements)

References 92 publications

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“…Studies dealing with the potential effects of fructose provided evidence that under condition of increase fructose intake, a state of increased promotion of oxidative stress is favored [22,23]. Interestingly, we have demonstrated that fructose-induced TF expression in human endothelial cells is mediated through production of oxygen free radicals and that the transcription factor NF-jB is the potential link in modulating these phenomena.…”

Section: Discussionmentioning

confidence: 92%

“…As it has been documented that fructose causes endothelial dysfunction through the generation of oxidative stress in endothelial cells [22,23], in another set of experiments, TF activity was evaluated as above but in HUVECs preincubated for 30 min in the presence of the free radical scavengers superoxide dismutase (SOD, 500 U/mL). Six different experiments were performed for each experimental condition.…”

Section: Effects Of Fructose On Tf Surface Expression and Activity Inmentioning

confidence: 99%

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Fructose induces prothrombotic phenotype in human endothelial cells

Cirillo

Pellegrino

Conte

et al. 2015

J Thromb Thrombolysis

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Intake of large amounts of added sweeteners has been associated with the pathogenesis of cardiometabolic risk. Several studies have shown that fructose increases the cardiovascular risk by modulating endothelial dysfunction and promoting atherosclerosis. Recently, a potential role for fructose in cardiovascular thrombosis has been suggested but with controversial results. Tissue factor (TF) plays a pivotal role in the pathophysiology of cardiovascular thrombosis by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of fructose, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk, on TF in human umbilical endothelial cells (HUVECs). Cells were stimulated with increasing concentrations of fructose (0.25, 1 and 2.5 mM) and then processed to evaluate TF-mRNA levels by real-time PCR as well as TF expression/activity by FACS analysis and procoagulant activity. Finally, a potential molecular pathway involved in modulating this phenomenon was investigated. We demonstrate that fructose induces transcription of mRNA for TF. In addition, we show that this monosaccharide promotes surface expression of TF that is functionally active. Fructose effects on TF appear modulated by the oxygen free radicals through activation of the transcription factor NF-κB since superoxide dismutase and NF-κB inhibitors suppressed TF expression. Data of the present study, although in vitro, indicate that fructose, besides promoting atherosclerosis, induces a prothrombotic phenotype in HUVECs, thus indicating one the mechanism(s) by which this sweetener might increase cardiometabolic risk.

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Section: Discussionmentioning

confidence: 92%

Section: Effects Of Fructose On Tf Surface Expression and Activity Inmentioning

confidence: 99%

Fructose induces prothrombotic phenotype in human endothelial cells

Cirillo

Pellegrino

Conte

et al. 2015

J Thromb Thrombolysis

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“…Moreover, macrophages play an important role in controlling the Th1/Th2 immune responses through the costimulating molecules CD80/CD86 and released cytokines (Bhargava and Lee, . These macrophages could produce inflammatory cytokines, such as IL-6 and TNFα, and induce insulin resistance in major metabolic tissues (Bhargava and Lee, 2012;Devaraj et al, 2010;Rajwani et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Pham

et al. 2016

Biomed Res Ther

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Introduction: Type 2 diabetes mellitus (T2D) is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, although T2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC) transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype.All patients were transfused with ADSCs at 1-2x10 6 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months). Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46), there was no contamination of mycoplasma, and endotoxin levels were low (<0.25 EU/mL). No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.

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“…UA is associated with endothelial dysfunction, which is aggravated by increased oxidative stress and inflammation [6]. Endothelial dysfunction is a manifestation of CRS, and is a maladapted endothelial phenotype characterized by reduced nitric oxide (NO) bioavailability, increased oxidative stress, elevated expression of pro-inflammatory and pro-thrombotic factors, and reduced endothelial-derived vasodilation [8]. However, the molecular mechanisms of fructose and UA on endothelial cell (EC) dysfunction and subsequently CRS are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Fructose and Uric Acid: Is There a Role in Endothelial Function?

et al. 2014

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Population level data support that consumption of fructose and fructose-based sweeteners has dramatically increased and suggest that high dietary intake of fructose is an important factor in the development of the cardiorenal metabolic syndrome (CRS). The CRS is a constellation of cardiac, kidney and metabolic disorders including insulin resistance, obesity, metabolic dyslipidemia, high blood pressure, and evidence of early cardiac and kidney disease. The consequences of fructose metabolism may result in intracellular ATP depletion, increased uric acid production, oxidative stress, inflammation, and increased lipogenesis, which are associated with endothelial dysfunction. Endothelial dysfunction is an early manifestation of vascular disease and a driver for the development of CRS. A better understanding of fructose overconsumption in the development of CRS may provide new insights into pathogenesis and future therapeutic strategies.

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Cell‐specific insulin resistance: implications for atherosclerosis

Cited by 18 publications

References 92 publications

Fructose induces prothrombotic phenotype in human endothelial cells

Fructose induces prothrombotic phenotype in human endothelial cells

Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

Fructose and Uric Acid: Is There a Role in Endothelial Function?

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