Journal ArticleDOI
Potential Role of TNF-α in the Pathogenesis of Insulin Resistance and Type 2 Diabetes
TLDR
Current evidence suggests that administration of exogenous TNF-alpha to animals can induce insulin resistance, whereas neutralization of T NF-alpha can improve insulin sensitivity, and it is still probable that TTF-alpha is a contributing factor in common metabolic disturbances such as insulin resistance and dyslipidemia.Abstract:
Tumor necrosis factor alpha (TNF-alpha) has well-described effects on lipid metabolism in the context of acute inflammation, as in sepsis. Recently, increased TNF-alpha production has been observed in adipose tissue derived from obese rodents or human subjects and TNF-alpha has been implicated as a causative factor in obesity-associated insulin resistance and the pathogenesis of type 2 diabetes. Thus, current evidence suggests that administration of exogenous TNF-alpha to animals can induce insulin resistance, whereas neutralization of TNF-alpha can improve insulin sensitivity. Importantly, results from knockout mice deficient in TNF-alpha or its receptors have suggested that TNF-alpha has a role in regulating in vivo insulin sensitivity. However, the absence of TNF-alpha action might only partially protect against obesity-induced insulin resistance in mice. Multiple mechanisms have been suggested to account for these metabolic effects of TNF-alpha. These include the downregulation of genes that are required for normal insulin action, direct effects on insulin signaling, induction of elevated free fatty acids via stimulation of lipolysis, and negative regulation of PPAR gamma, an important insulin-sensitizing nuclear receptor. Although current evidence suggests that neutralizing TNF-alpha in type 2 diabetic subjects is not sufficient to cause metabolic improvement, it is still probable that TNF-alpha is a contributing factor in common metabolic disturbances such as insulin resistance and dyslipidemia.read more
Citations
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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
The hormone resistin links obesity to diabetes
Claire M. Steppan,Shannon T. Bailey,Savitha Bhat,Elizabeth J. Brown,Ronadip R. Banerjee,Christopher M. Wright,Hiralben R. Patel,Rexford S. Ahima,Mitchell A. Lazar +8 more
TL;DR: It is shown that adipocytes secrete a unique signalling molecule, which is named resistin (for resistance to insulin), which circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity.
Journal ArticleDOI
Type 2 diabetes - principles of pathogenesis and therapy
TL;DR: Type 2 diabetes mellitus has a strong genetic component, but only a handful of genes have been identified so far: genes for calpain 10, potassium inward-rectifier 6.2, peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and others.
Journal ArticleDOI
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
TL;DR: A unifying hypothesis is proposed whereby hyperglycemia and FFA-induced activation of the nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases stress pathways plays a key role in causing late complications in type 1 and type 1 diabetes, along with insulin resistance and impaired insulin secretion in type 2 diabetes.
Journal ArticleDOI
Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
Dongsheng Cai,Minsheng Yuan,Daniel Frantz,Daniel Frantz,Peter A. Melendez,Peter A. Melendez,Lone Hansen,Jongsoon Lee,Steven E. Shoelson +8 more
TL;DR: It is shown that lipid accumulation in the liver leads to subacute hepatic 'inflammation' through NF-κB activation and downstream cytokine production, which causes insulin resistance both locally in liver and systemically.
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.
Journal ArticleDOI
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TL;DR: Results indicate that TNF-α induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
Journal ArticleDOI
Protection from obesity-induced insulin resistance in mice lacking TNF-|[alpha]| function
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Journal ArticleDOI
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