Chronic reactive oxygen species exposure inhibits glucose uptake and causes insulin resistance in C2C12 myotubes

Ding, Hongwen; Heng, Baoli; He, Wenfang; Shi, Liping; Lai, Caiyong; Xiao, Long; Ren, Haolin; Mo, Shijie; Su, Zexuan

doi:10.1016/j.bbrc.2016.08.028

Cited by 32 publications

(19 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enhanced H 2 O 2 production has also been shown to occur in skeletal muscle of men fed a high-fat diet [13], and of obese, insulin-resistant women with polycystic ovary syndrome [36]. In vitro , H 2 O 2 exposure impairs insulin signaling by various mechanisms including suppression of insulin-induced Akt phosphorylation, and inhibition of both transcription of glucose transporter 4 (GLUT 4) and its translocation to the cell membrane [37, 38]. …”

Section: Discussionmentioning

confidence: 99%

Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: Association with insulin resistance

et al. 2017

View full text Add to dashboard Cite

ObjectiveAlthough adipose tissue hydrogen peroxide (H2O2) and its metabolizing enzymes have been linked to obesity and insulin resistance in animal studies, this relation remains to be evaluated in humans.MethodsNon-diabetic men (N = 43, median age, 49 (37, 54 y)) undergoing abdominal surgeries were studied. Participants were classified by body mass index (BMI) into normal-weight (N = 19), or overweight/obese (Ow/Ob; BMI ≥25; N = 24). Centrally obese men were identified by waist-height ratio ≥0.5. H2O2 and activities of superoxide dismutase, catalase and glutathione peroxidase enzymes were assayed in subcutaneous fat samples, and visceral fat (available from N = 33), and their associations with anthropometric parameters, fasting serum lipids, and the homeostasis model of insulin resistance (HOMA-IR) were tested using correlations and multivariate linear regression.ResultsH2O2 concentrations and catalase activity were increased in visceral fat from Ow/Ob men, compared to normal-weight subjects (+32%, P = 0.038 and +51%, P = 0.043 respectively). Centrally obese subjects had >2-fold higher superoxide dismutase activity (P = 0.005), 46% higher H2O2 (P = 0.028), and 89% higher catalase activity (P = 0.009) in visceral fat, compared to lean subjects. Central obesity did not alter these markers in subcutaneous fat, apart from a 50% increase in catalase, and did not affect glutathione peroxidase in either fat depot. H2O2 in visceral fat positively correlated with insulin resistance (r = 0.40, P = 0.032). Catalase activity in visceral fat was an independent determinant of HOMA-IR, explaining ~18% of the variance (ß = 0.42, P = 0.016), after adjustment for age and BMI.ConclusionThese findings suggest that adipose tissue catalase shows compensatory up-regulation in response to obesity-induced H2O2 accumulation, and that perturbed H2O2 metabolism in visceral fat is linked to insulin resistance in obese humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: Association with insulin resistance

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The results of the present study showed that the higher levels of the myocardial damage-associated proteins p-PERK and CHOP in the cardiac muscle of high fat diet-induced obese middle-aged rats could be significantly reduced by 8 weeks of intermittent ladder-climbing exercise training. High fat diet increases the production of mitochondrial ROS which is clearly associated with insulin resistance [ 56 57 58 59 ]. Reactive oxygen species (ROS) has been identified as crucial regulators of ER function and unfolded protein response activation (UPR), ER stress occur concurrently with an increased ROS production [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and endoplasmic reticulum stress of the cardiac muscle in obese middle-aged rats

Kim

Ahn

Jung

et al. 2017

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

The aim of this study is to investigate the effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and ER stress of the cardiac muscle in high fat diet-induced obese middle-aged rats. We induced obesity over 6 weeks of period in 40 male Sprague-Dawley rats around 50 weeks old, and were randomly divided into four experimental groups: chow, HFD, exercise+HFD, and exercise+chow. The exercising groups underwent high-intensity intermittent training using a ladder-climbing and weight exercise 3 days/week for a total of 8 weeks. High-fat diet and concurrent exercise resulted in no significant reduction in body weight but caused a significant reduction in visceral fat weight (p<0.05). Expression of PPARδ increased in the exercise groups and was significantly increased in the high-fat diet+exercise group (p<0.05). Among the ER stress-related proteins, the expression levels of p-PERK and CHOP, related to cardiac muscle damage, were significantly higher in the cardiac muscle of the high-fat diet group (p<0.05), and were significantly reduced by intermittent ladder-climbing exercise training (p<0.05). Specifically, this reduction was greater when the rats underwent exercise after switching back to the chow diet with a reduced caloric intake. Collectively, these results suggest that the combination of intermittent ladder-climbing exercise training and a reduced caloric intake can decrease the levels of ER stress-related proteins that contribute to cardiac muscle damage in obesity and aging. However, additional validation is required to understand the effects of these changes on mitochondrial biogenesis during exercise.

show abstract

“…C2C12 myotubes are derived from the fusion of C2C12 myoblasts that adopt a multinuclear tubular cell shape 28 . These cells are difficult to be transfected with DNA vectors.…”

Section: Discussionmentioning

confidence: 99%

“…The second objective of this study was to achieve the expression of the biosensor HyPer in myotubes. Myotubes are differentiated skeletal muscle cells that are formed from the fusion of C2C12 myoblasts, which generate multinucleated cells with a tubular morphology 28 . During the embryonic development of skeletal muscle, the myotube is an intermediate cellular state between the myoblast and the mature skeletal muscle fibre 29 .…”

Section: Hyper Expression In C2c12 Myotubesmentioning

confidence: 99%

Expression and functional analysis of the hydrogen peroxide biosensors HyPer and HyPer2 in C2C12 myoblasts/myotubes and single skeletal muscle fibres

Fernández-Puente

Sánchez-Martı́n

Andrés

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Hydrogen peroxide (H2O2) is generated in cells and plays an important role as a signalling molecule. It has been reported that H2O2 is involved in physiological and pathological processes in skeletal muscle. However, H2O2 detection in cells with traditional techniques produces frequent artefacts. Currently, the HyPer biosensor detects intracellular H2O2 specifically in real time using fluorescence microscopy. The aim of this study was to develop and optimize approaches used to express the HyPer biosensor in different models of skeletal muscle cells, such as the C2C12 myoblast/myotube cell line and mature skeletal muscle fibres isolated from C57BL/6J mice, and to measure intracellular H2O2 in real time in these cells. The results show that the expression of the HyPer biosensor in skeletal muscle cells is possible. In addition, we demonstrate that HyPer is functional and that this biosensor detects changes and fluctuations in intracellular H2O2 in a reversible manner. The HyPer2 biosensor, which is a more advanced version of HyPer, presents improved properties in terms of sensitivity in detecting lower concentrations of H2O2 in skeletal muscle fibres. In conclusion, the expression of the HyPer biosensor in the different experimental models combined with fluorescence microscopy techniques is a powerful methodology to monitor and register intracellular H2O2 specifically in skeletal muscle. The innovation of the methodological approaches presented in this study may present new avenues for studying the role of H2O2 in skeletal muscle pathophysiology. Furthermore, the methodology may potentially be adapted to yield other specific biosensors for different reactive oxygen and nitrogen species or metabolites involved in cellular functions.

show abstract

Chronic reactive oxygen species exposure inhibits glucose uptake and causes insulin resistance in C2C12 myotubes

Cited by 32 publications

References 20 publications

Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: Association with insulin resistance

Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: Association with insulin resistance

Effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and endoplasmic reticulum stress of the cardiac muscle in obese middle-aged rats

Expression and functional analysis of the hydrogen peroxide biosensors HyPer and HyPer2 in C2C12 myoblasts/myotubes and single skeletal muscle fibres

Contact Info

Product

Resources

About