PMID- 17481767
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20131121
IS  - 0168-8227 (Print)
IS  - 0168-8227 (Linking)
VI  - 77 Suppl 1
DP  - 2007 Sep
TI  - Impact of mitochondrial ROS production in the pathogenesis of insulin resistance.
PG  - S161-4
AB  - Tumor necrosis factor-alpha (TNF-alpha) inhibits insulin action, in part, by 
      activating c-jun NH(2)-terminal kinases (JNK). However, the precise mechanisms by 
      which TNF-alpha activates JNK are unknown. Recently, we confirmed that 
      hyperglycemia increased mitochondrial reactive oxygen species (ROS) production, 
      and which can associate with the pathogenesis of diabetic vascular complications. 
      In addition, apoptosis signal-regulating kinase 1 (ASK1) was reported to activate 
      the JNK and p38 signaling pathways and is required for TNF-alpha-induced 
      apoptosis. Here we demonstrate that TNF-alpha increases mitochondrial ROS 
      production and ASK1 activity, and that these TNF-alpha-induced phenomena 
      associate with JNK activation, increase in Ser(307) phosphorylation of IRS-1 and 
      decrease in insulin-stimulated tyrosine phosphorylation of IRS-1, all of which 
      are believed to be the molecular basis of TNF-alpha-induced insulin resistance. 
      We claim that mitochondrial ROS production may be a key factor not only in 
      diabetic vascular complications, but also in the development of type 2 diabetes. 
      This integrating paradigm could provide a new conceptual framework for further 
      research and therapies for the treatment of type 2 diabetes.
FAU - Nishikawa, Takeshi
AU  - Nishikawa T
AD  - Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, 
      Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. 
      takeshi@kaiju.medic.kumamoto-u.ac.jp
FAU - Kukidome, Daisuke
AU  - Kukidome D
FAU - Sonoda, Kazuhiro
AU  - Sonoda K
FAU - Fujisawa, Kazuo
AU  - Fujisawa K
FAU - Matsuhisa, Takako
AU  - Matsuhisa T
FAU - Motoshima, Hiroyuki
AU  - Motoshima H
FAU - Matsumura, Takeshi
AU  - Matsumura T
FAU - Araki, Eiichi
AU  - Araki E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070503
PL  - Ireland
TA  - Diabetes Res Clin Pract
JT  - Diabetes research and clinical practice
JID - 8508335
RN  - 0 (Insulin)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Glucose/pharmacology
MH  - Humans
MH  - Hyperglycemia/physiopathology
MH  - Insulin/physiology
MH  - Insulin Resistance/*physiology
MH  - Mitochondria/drug effects/*metabolism
MH  - Models, Biological
MH  - Reactive Oxygen Species/*metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology/physiology
EDAT- 2007/05/08 09:00
MHDA- 2007/11/14 09:00
CRDT- 2007/05/08 09:00
PHST- 2007/01/29 00:00 [accepted]
PHST- 2007/05/08 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/05/08 09:00 [entrez]
AID - S0168-8227(07)00181-7 [pii]
AID - 10.1016/j.diabres.2007.01.071 [doi]
PST - ppublish
SO  - Diabetes Res Clin Pract. 2007 Sep;77 Suppl 1:S161-4. doi: 
      10.1016/j.diabres.2007.01.071. Epub 2007 May 3.