NOD2 activation induces oxidative stress contributing to mitochondrial dysfunction and insulin resistance in skeletal muscle cells

2015 ◽  
Vol 89 ◽  
pp. 158-169 ◽  
Author(s):  
Chandan K. Maurya ◽  
Deepti Arha ◽  
Amit K. Rai ◽  
Shashi Kant Kumar ◽  
Jyotsana Pandey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

scholarly journals SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells

2015 ◽  
Vol 240 (5) ◽  
pp. 557-565 ◽  
Author(s):  
Hao-Hao Zhang ◽  
Xiao-Jun Ma ◽  
Li-Na Wu ◽  
Yan-Yan Zhao ◽  
Peng-Yu Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

scholarly journals Nicorandil attenuates high glucose-induced insulin resistance by suppressing oxidative stress-mediated ER stress PERK signaling pathway

2021 ◽  
Vol 9 (1) ◽  
pp. e001884
Author(s):  
Zhongwei Liu ◽  
Haitao Zhu ◽  
Chunhui He ◽  
Ting He ◽  
Shuo Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Er Stress ◽  
High Glucose ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

IntroductionGlucose-induced insulin resistance is a typical character of diabetes. Nicorandil is now widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress, which are involved in insulin resistance. Here, we investigated mechanisms of nicorandil’s novel pharmacological activity on insulin resistance in diabetes.Research design and methodsNicorandil was administrated to streptozotocin-induced animals with diabetes and high glucose exposed skeletal muscle cells. Insulin resistance and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress signaling activation and glucose uptake were assessed.ResultsNicorandil attenuated high glucose-induced insulin resistance without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in rats with diabetes. Nicorandil treatment suppressed protein kinase C/nicotinamide adenine dinucleotide phosphate oxidases system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress-mediated ER stress protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α/activating transcription factor 4/CEBP homologous protein/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil downregulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells.ConclusionsBy reducing cytoplasmic calcium, nicorandil alleviated high glucose-induced insulin resistance by inhibiting oxidative stress-mediated ER stress PERK pathway.

scholarly journals Glutathione Peroxidase 3 Mediates the Antioxidant Effect of Peroxisome Proliferator-Activated Receptor γ in Human Skeletal Muscle Cells

2008 ◽  
Vol 29 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Sung Soo Chung ◽  
Min Kim ◽  
Byoung-Soo Youn ◽  
Nam Seok Lee ◽  
Ji Woo Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Human Skeletal Muscle Cells

ABSTRACT Oxidative stress plays an important role in the pathogenesis of insulin resistance and type 2 diabetes mellitus and in diabetic vascular complications. Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor γ (PPARγ) agonists, improve insulin sensitivity and are currently used for the treatment of type 2 diabetes mellitus. Here, we show that TZD prevents oxidative stress-induced insulin resistance in human skeletal muscle cells, as indicated by the increase in insulin-stimulated glucose uptake and insulin signaling. Importantly, TZD-mediated activation of PPARγ induces gene expression of glutathione peroxidase 3 (GPx3), which reduces extracellular H2O2 levels causing insulin resistance in skeletal muscle cells. Inhibition of GPx3 expression prevents the antioxidant effects of TZDs on insulin action in oxidative stress-induced insulin-resistant cells, suggesting that GPx3 is required for the regulation of PPARγ-mediated antioxidant effects. Furthermore, reduced plasma GPx3 levels were found in patients with type 2 diabetes mellitus and in db/db/DIO mice. Collectively, these results suggest that the antioxidant effect of PPARγ is exclusively mediated by GPx3 and further imply that GPx3 may be a therapeutic target for insulin resistance and diabetes mellitus.

Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress

APOPTOSIS ◽  
2015 ◽  
Vol 20 (7) ◽  
pp. 930-947 ◽  
Author(s):  
Natasha Jaiswal ◽  
Chandan K. Maurya ◽  
Deepti Arha ◽  
Deepa R. Avisetti ◽  
Ayyappan Prathapan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Muscle Cells ◽  
Skeletal Muscle Cells

scholarly journals Oxidative stress-induced insulin resistance in skeletal muscle cells is ameliorated by gamma-tocopherol treatment

2008 ◽  
Vol 47 (7) ◽  
pp. 387-392 ◽  
Author(s):  
Indu Singh ◽  
Andrew L. Carey ◽  
Nadine Watson ◽  
Mark A. Febbraio ◽  
John A. Hawley
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Gamma Tocopherol

Mitofusin 2 deficiency leads to oxidative stress that contributes to insulin resistance in rat skeletal muscle cells

2014 ◽  
Vol 41 (10) ◽  
pp. 6975-6983 ◽  
Author(s):  
Qian Nie ◽  
Chao Wang ◽  
Guangyao Song ◽  
Huijuan Ma ◽  
Dexian Kong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Rat Skeletal Muscle ◽  
Mitofusin 2

Extracts of Hymenocardia acida ameliorate insulin resistance in skeletal muscle cells

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
II Ezeigbo ◽  
C Wheeler-Jones ◽  
S Gibbons ◽  
ME Cleasby
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Ameliorate Insulin Resistance

scholarly journals Adiponectin improves insulin sensitivity via activation of autophagic flux

2017 ◽  
Vol 59 (4) ◽  
pp. 339-350 ◽  
Author(s):  
Penny Ahlstrom ◽  
Esther Rai ◽  
Suharto Chakma ◽  
Hee Ho Cho ◽  
Palanivel Rengasamy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Er Stress ◽  
Western Blotting ◽  
Muscle Cells ◽  
Dominant Negative ◽  
Skeletal Muscle Cells ◽  
Dominant Negative Mutant ◽  
Autophagic Flux

Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, and one potential causative cellular mechanism is endoplasmic reticulum (ER) stress. Adiponectin mediates anti-diabetic effects via direct metabolic actions and by improving insulin sensitivity, and we recently demonstrated an important role in stimulation of autophagy by adiponectin. However, there is limited knowledge on crosstalk between autophagy and ER stress in skeletal muscle and in particular how they are regulated by adiponectin. Here, we utilized the model of high insulin/glucose (HIHG)-induced insulin resistance, determined by measuring Akt phosphorylation (T308 and S473) and glucose uptake in L6 skeletal muscle cells. HIHG reduced autophagic flux measured by LC3 and p62 Western blotting and tandem fluorescent RFP/GFP-LC3 immunofluorescence (IF). HIHG also induced ER stress assessed by thioflavin T/KDEL IF, pIRE1, pPERK, peIF2α and ATF6 Western blotting and induction of a GRP78-mCherry reporter. Induction of autophagy by adiponectin or rapamycin attenuated HIHG-induced ER stress and improved insulin sensitivity. The functional significance of enhanced autophagy was validated by demonstrating a lack of improved insulin sensitivity in response to adiponectin in autophagy-deficient cells generated by overexpression of dominant negative mutant of Atg5. In summary, adiponectin-induced autophagy in skeletal muscle cells alleviated HIHG-induced ER stress and insulin resistance.

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