The role of TNFα and TNF receptors in obesity and insulin resistance
Reads0
Chats0
TLDR
The role of TNFα and TNF receptors in obesity and insulin resistance and the potential role of “cell reprograming” in this situation is still under investigation.Abstract:
Insulin resistance, a smaller than expected response to a given dose of insulin, is associated with many common diseases including, ageing, polycystic ovarian disease, syndrome X, cancer, infections, trauma and, most significantly, obesity and type 2 diabetes mellitus. The biochemical basis of insulin resistance in type 2 diabetes has been the subject of many studies. Earlier studies have indicated that quantitative regulation of the insulin sensitive glucose transporters (Glut-4) and insulin receptors themselves may contribute to this disorder, however, these two factors are probably inadequate to explain the extent of insulin resistance. This point also became apparent by the development of only mild hyperinsulinaemia in mice with a targeted mutation in the Glut-4 gene. Studies on postreceptor defects in type 2 diabetes has recently focused on the intrinsic catalytic activity of the insulin receptor and downstream signalling events. A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in both animal and human type 2 diabetes. Importantly, this appears to occur in all of the major insulin-sensitive tissues, namely the muscle, fat and liver. It is now clear that decreased signalling capacity of the insulin receptor is an important component of this disease. I will review some of the potential mechanisms underlying this deficiency.read more
Citations
More filters
Journal ArticleDOI
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Toshimasa Yamauchi,Junji Kamon,Hironori Waki,Yasuo Terauchi,Naoto Kubota,Kazuo Hara,Y. Mori,Tomohiro Ide,Kouji Murakami,Nobuyo Tsuboyama-Kasaoka,Osamu Ezaki,Y. Akanuma,Oksana Gavrilova,Charles Vinson,Marc L. Reitman,Hiroyuki Kagechika,Koichi Shudo,Madoka Yoda,Yasuko Nakano,Kazuyuki Tobe,R. Nagai,Shigeko Kimura,Motowo Tomita,Philippe Froguel,Takashi Kadowaki +24 more
TL;DR: It is concluded that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy and that the replenishment of adiponECTin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
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
Obesity and insulin resistance
Barbara B. Kahn,Jeffrey S. Flier +1 more
TL;DR: Recent progress in understanding of the adipo-insulin axis is reviewed, areas of controversy or uncertainty are highlighted, and approaches to clarifying the unresolved issues are suggested.
Journal ArticleDOI
Adiponectin and Adiponectin Receptors
TL;DR: It is shown that AdipoR1 and AdIPoR2 serve as receptors for globular and full-length adiponectin and mediate increased AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha ligand activities, and glucose uptake and fatty-acid oxidation by adiponECTin.
Journal ArticleDOI
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
More filters
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
Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.
TL;DR: A role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance is suggested as well as the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA.
Journal ArticleDOI
IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin Resistance
Gökhan S. Hotamisligil,Pascal Peraldi,Adriane I. Budavari,Ramsey Ellis,Morris F. White,Bruce M. Spiegelman +5 more
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
TL;DR: Results indicate that TNF-α is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action.
Journal ArticleDOI
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
TL;DR: Continuously elevated levels of plasma FFAs may play a key role in the pathogenesis of NIDDM in predisposed individuals by impairing peripheral glucose utilization and by promoting hepatic glucose overproduction.
Related Papers (5)
Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance
The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity
Toshimasa Yamauchi,Junji Kamon,Hironori Waki,Yasuo Terauchi,Naoto Kubota,Kazuo Hara,Y. Mori,Tomohiro Ide,Kouji Murakami,Nobuyo Tsuboyama-Kasaoka,Osamu Ezaki,Y. Akanuma,Oksana Gavrilova,Charles Vinson,Marc L. Reitman,Hiroyuki Kagechika,Koichi Shudo,Madoka Yoda,Yasuko Nakano,Kazuyuki Tobe,R. Nagai,Shigeko Kimura,Motowo Tomita,Philippe Froguel,Takashi Kadowaki +24 more
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.
Yukio Arita,Shinji Kihara,Noriyuki Ouchi,Masahiko Takahashi,Kazuhisa Maeda,Jun-ichiro Miyagawa,Kikuko Hotta,Iichiro Shimomura,Tadashi Nakamura,Koji Miyaoka,Hiroshi Kuriyama,Makoto Nishida,Shizuya Yamashita,Kosaku Okubo,Kenji Matsubara,Masahiro Muraguchi,Yasuichi Ohmoto,Tohru Funahashi,Yuji Matsuzawa +18 more