Journal ArticleDOI
Reactive oxygen species have a causal role in multiple forms of insulin resistance.
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TLDR
A genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-α and the other with the glucocorticoid dexamethasone, suggests that reactive oxygen species levels are increased in both models, and increased ROS levels are an important trigger for insulin resistance in numerous settings.Abstract:
Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.read more
Citations
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Inflammation and metabolic disorders
TL;DR: Dysfunction of the immune response and metabolic regulation interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease.
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Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
Patrice D. Cani,Rodrigo Bibiloni,Claude Knauf,Aurélie Waget,Audrey M. Neyrinck,Nathalie M. Delzenne,Rémy Burcelin +6 more
TL;DR: It is found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice, demonstrating that changes in gut microbiota controls metabolic endotoxinemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability.
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Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease
TL;DR: The endoplasmic reticulum is the major site in the cell for protein folding and trafficking and is central to many cellular functions and is emerging as a potential site for the intersection of inflammation and metabolic disease.
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Selenium and human health
TL;DR: The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional seenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenum supplements.
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Adipocytes as regulators of energy balance and glucose homeostasis
TL;DR: Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways as discussed by the authors.
References
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TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Journal Article
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
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TL;DR: In this article, the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.
Journal ArticleDOI
Significance analysis of microarrays applied to the ionizing radiation response
TL;DR: A method that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements is described, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.
Journal ArticleDOI
Obesity is associated with macrophage accumulation in adipose tissue
Stuart P. Weisberg,Daniel McCann,Manisha Desai,Michael Rosenbaum,Rudolph L. Leibel,Anthony W. Ferrante +5 more
TL;DR: Transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob) found that the expression of 1,304 transcripts correlated significantly with body mass.
Journal ArticleDOI
Biochemistry and molecular cell biology of diabetic complications
TL;DR: This integrating paradigm provides a new conceptual framework for future research and drug discovery in diabetes-specific microvascular disease and seems to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain.