Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

Maddux, Betty A.; See, Wendy; Lawrence, John C.; Goldfine, Amy L.; Goldfine, Ira D.; Evans, Joseph L

doi:10.2337/diabetes.50.2.404

Cited by 352 publications

(262 citation statements)

References 53 publications

(62 reference statements)

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“…Mitochondrial ROS release and the effect of training Previous studies have suggested that increased cytosolic concentration of free radicals have an inhibitory effect on the insulin signalling cascade [16]. A main purpose of the present study was to investigate the hypothesis that insulin resistance is associated with increased mitochondrial ROS release.…”

Section: Discussionmentioning

confidence: 92%

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Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

et al. 2010

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Aim/hypothesis Studies have suggested a link between insulin resistance and mitochondrial dysfunction in skeletal muscles. Our primary aim was to investigate the effect of aerobic training on mitochondrial respiration and mitochondrial reactive oxygen species (ROS) release in skeletal muscle of obese participants with and without type 2 diabetes. Methods Type 2 diabetic men (n=13) and control (n=14) participants matched for age, BMI and physical activity completed 10 weeks of aerobic training. Pre-and posttraining muscle biopsies were obtained before a euglycaemichyperinsulinaemic clamp and used for measurement of respiratory function and ROS release in isolated mitochondria. Results Training significantly increased insulin sensitivity, maximal oxygen consumption and muscle mitochondrial respiration with no difference between groups. When expressed in relation to a marker of mitochondrial density (intrinsic mitochondrial respiration), training resulted in increased mitochondrial ADP-stimulated respiration (with NADH-generating substrates) and decreased respiration without ADP. Intrinsic mitochondrial respiration was not different between groups despite lower insulin sensitivity in type 2 diabetic participants. Mitochondrial ROS release tended to be higher in participants with type 2 diabetes. Conclusions/interpretation Aerobic training improves muscle respiration and intrinsic mitochondrial respiration in untrained obese participants with and without type 2 diabetes. These adaptations demonstrate an increased metabolic fitness, but do not seem to be directly related to training-induced changes in insulin sensitivity.

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Section: Discussionmentioning

confidence: 92%

“…In cultured cells there is experimental evidence that ROS have an inhibitory effect on insulin signalling [16,17]. Human studies have shown that obesity and high-fat diet increase mitochondrial hydrogen peroxide release [18].…”

Section: Introductionmentioning

confidence: 99%

Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

et al. 2010

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“…The biological responses of various cultured cells to insulin have been shown to be impaired by micromolar H 2 O 2 concentrations [29±32, 39]. In cells representing the metabolic target tissues of insulin such as 3T3-L1 adipocytes, this effect of oxidative stress causes insulin resistance, including impaired insulin-stimulated glucose uptake activity [29,30,39]. The mechanisms underlying this phenomenon appear to be complex and depend on the duration and intensity of the oxidative insult.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress impairs nuclear proteins binding to the insulin responsive element in the GLUT4 promoter

2001

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Accumulating experimental evidence suggests that the expression of the insulin responsive glucose transporter GLUT4 could be central in determining peripheral insulin sensitivity and thus could be an important factor in the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus [1,2]. Various groups have shown that GLUT4 expression in adipose tissue is reduced in obese, non-diabetic subjects, and more so in Type II diabetic patients [3,4]. Studies in animal models of diabetes have also measured GLUT4 mRNA content and its transcription rate in adipose tissue, mostly showing a role for transcriptional regulation of the GLUT4 gene [5±8]. Moreover, a causative role for decreased adipose tissue GLUT4 expression in the diabetic phenotype has been suggested. Disruption of a single allele of the GLUT4 gene caused a decrease in adipocyte Diabetologia (2001) Abstract Aims/hypothesis. Substantial evidence suggests an important role for the expression of GLUT4 in adipocytes, in the pathogenesis of insulin resistance and Type II (non-insulin-dependent) diabetes mellitus. We investigated whether oxidative stress decreases GLUT4 expression by impairing DNA binding of nuclear proteins to the insulin responsive element in the GLUT4 promoter.Methods. 3T3-L1 adipocytes were exposed to micromolar H 2 O 2 concentrations and GLUT4 expression and binding of nuclear proteins to defined DNA sequences were assessed. Results. GLUT4 mRNA was decreased after at least 4 h exposure to H 2 O 2 , without a major change in the stability of GLUT4 transcripts. Nuclear protein extracts prepared from oxidized cells showed decreased binding to the insulin responsive element of the GLUT4 promoter but not to other DNA sequences.The direct effect of oxidation on the binding to the insulin response element was shown by the observation that in vitro oxidation of nuclear extracts with H 2 O 2 , n-ethylmaleimide or diamide decreased protein-DNA complex formation. This, and decreased binding capacity observed in nuclear extracts from oxidized cells, were partly reversible by subsequent treatment with a reducing agent. Protein binding to a consensus DNA sequence for nuclear factor 1 transcription factors was decreased 16 % by oxidation, whereas no change was observed in the protein content of several isoforms of these proteins. Conclusion/interpretation. Oxidative stress causes decreased GLUT4 expression, associated with impaired binding of nuclear proteins to the insulin responsive element in the GLUT4 promoter. [Diabetologia (2001

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“…Oxidative/nitrosative stress may have a serious impact on cell viability and induce cellular responses leading to cell death (3). Many studies have shown a connection between oxidative molecular damage and pathophysiological mechanisms associated with severe diseases such as atherosclerosis (4), neurodegenerative disorders (5), and diabetes, and an important role in the etiopathogenesis of inflammatory diseases (6). There is also a relationship between oxidative stress and aging processes (7).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of salivary oxidative parameters in overweight and obese young adults

Chielle

Casarin

2017

Arch. Endocrinol. Metab.

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Background: Obesity is characterized by a deposition of abnormal or excessive fat in adipose tissue, and is linked with a risk of damage to several metabolic and pathological processes associated with oxidative stress. To date, salivary oxidative biomarkers have been minimally explored in obese individuals. Thus, the aim of this study was to assess the concentrations of salivary oxidative biomarkers (ferric-reducing antioxidant power, uric acid, sulfhydryl groups) and lipid peroxidation in obese and overweight young subjects. Materials and methods: Levels of lipid peroxidation, ferricreducing antioxidant power, uric acid, and SH groups were determined in the saliva and serum of 149 young adults, including 54 normal weight, 27 overweight, and 68 obese individuals. Anthropometric measurements were also evaluated. Results: Salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, as well as serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation were higher in obese patients when compared with individuals with normal weight. There were correlations between salivary and serum ferric-reducing antioxidant power and salivary and serum uric acid in the obese and normal-weight groups. Conclusions: Our results indicate that the increase in salivary levels of ferric-reducing antioxidant power, sulfhydryl groups, and lipid peroxidation, and serum levels of ferric-reducing antioxidant power, uric acid, and lipid peroxidation could be related to the regulation of various processes in the adipose tissue. These findings may hold promise in identifying new oxidative markers to assist in diagnosing and monitoring overweight and obese patients. Arch Endocrinol Metab. 2017;61(2):152-9.

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Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

Cited by 352 publications

References 53 publications

Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes

Oxidative stress impairs nuclear proteins binding to the insulin responsive element in the GLUT4 promoter

Evaluation of salivary oxidative parameters in overweight and obese young adults

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