Journal ArticleDOI
Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of Ikkβ
Minsheng Yuan,Nicky Konstantopoulos,Jongsoon Lee,Lone Hansen,Zhi-Wei Li,Michael Karin,Steven E. Shoelson +6 more
TLDR
It is shown that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling and identifies the IKKβ pathway as a target for insulin sensitization.Abstract:
We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.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.
Journal ArticleDOI
Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
Haiyan Xu,Glenn Barnes,Qing Yang,Guo Tan,Daseng Yang,Chieh J. Chou,Jason Sole,Andrew Nichols,Jeffrey S. Ross,Louis A. Tartaglia,Hong Chen +10 more
TL;DR: It is proposed that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue, and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance.
Journal ArticleDOI
Insulin signalling and the regulation of glucose and lipid metabolism
Alan R. Saltiel,C. Ronald Kahn +1 more
TL;DR: The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide, and tissues such as muscle, fat and liver become less responsive or resistant to insulin.
Journal ArticleDOI
Inflammation and insulin resistance
TL;DR: The evolving concept of insulin resistance and T2D as having immunological components and an improving picture of how inflammation modulates metabolism provide new opportunities for using antiinflammatory strategies to correct the metabolic consequences of excess adiposity.
Journal ArticleDOI
Inflammation, stress, and diabetes
TL;DR: The molecular and cellular underpinnings of obesity-induced inflammation and the signaling pathways at the intersection of metabolism and inflammation that contribute to diabetes are discussed.
References
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Journal ArticleDOI
Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance
TL;DR: A role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity is indicated.
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Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS)
Andreas Festa,Ralph B. D'Agostino,George Howard,Leena Mykkänen,Russell P. Tracy,Steven M. Haffner +5 more
TL;DR: In this article, the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of the insulin resistance syndrome (IRS) in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), was investigated.
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A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
TL;DR: IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-κB activation, and phosphorylates IκBs on the sites that trigger their degradation.
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The IκB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKβ, Necessary for IκB Phosphorylation and NF-κB Activation
TL;DR: The molecular cloning and characterization of IKKbeta, a second subunit of the IKK complex, is described, which is 50% identical to IKKalpha and like it contains a kinase domain, a leucine zipper, and a helix-loop-helix.
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Inhibition of NF-kappa B by sodium salicylate and aspirin
Elizabeth Kopp,Sankar Ghosh +1 more
TL;DR: The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B, which further explains the mechanism of action of these drugs.