A central role for JNK in obesity and insulin resistance.

Abstract	Obesity is closely associated with insulin resistance and establishes the leading risk factor for type 2 diabetes mellitus, yet the molecular mechanisms of this association are poorly understood. The c-Jun amino-terminal kinases (JNKs) can interfere with insulin action in cultured cells and are activated by inflammatory cytokines and free fatty acids, molecules that have been implicated in the development of type 2 diabetes. Here we show that JNK activity is abnormally elevated in obesity. Furthermore, an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity. Thus, JNK is a crucial mediator of obesity and insulin resistance and a potential target for therapeutics.
Authors	Jiro Hirosumi, Gürol Tuncman, Lufen Chang, Cem Z Görgün, K Teoman Uysal, Kazuhisa Maeda, Michael Karin, Gökhan S Hotamisligil
Journal	Nature (Nature) Vol. 420 Issue 6913 Pg. 333-6 (Nov 21 2002) ISSN: 0028-0836 [Print] England
PMID	12447443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Blood Glucose Insulin Insulin Receptor Substrate Proteins Irs1 protein, mouse Phosphoproteins Mitogen-Activated Protein Kinase 9 Receptor, Insulin Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinases
Topics	Adipose Tissue (enzymology, metabolism, physiopathology) Animals Blood Glucose (metabolism) Diabetes Mellitus, Type 2 (complications, enzymology, genetics, physiopathology) Diet Disease Models, Animal Gene Deletion Homeostasis Hyperinsulinism (complications, enzymology, genetics, physiopathology) Insulin (pharmacology) Insulin Receptor Substrate Proteins Insulin Resistance (genetics, physiology) Lipid Metabolism Mice Mice, Knockout Mice, Obese Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinase 9 Mitogen-Activated Protein Kinases (deficiency, genetics, metabolism) Obesity (complications, enzymology, genetics, physiopathology) Phosphoproteins (metabolism) Phosphorylation Receptor, Insulin (metabolism) Signal Transduction (drug effects)

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