title: JNK: bridging the insulin signaling and inflammatory pathway.
abstract: Obesity and insulin resistance are strongly associated with systemic markers of inflammation and endoplasmic reticulum stress. c-Jun N-terminal kinases (JNK) are activated by inflammatory cytokines and have a key role in beta-cell apoptosis and in negative regulation of insulin signaling. JNK1-deficient mice are protected from diet-induced obesity and insulin resistance, while genetically obese mice with targeted mutations in JNK1 are leaner and have reduced insulin and blood glucose levels. These studies validate JNK as a link between inflammation and metabolic diseases and as a promising drug target. This review highlights recent advances in small-molecule inhibitors of JNK that have also been targeted for other diseases with an inflammatory component such as stroke, rheumatoid arthritis, and Alzheimer's and Parkinson's diseases.
authors.affiliation: Abbott Laboratories, Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Rondinone
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis*; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases