title: cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance.
abstract: The cJun NH(2)-terminal kinase isoform JNK1 is implicated in the mechanism of obesity-induced insulin resistance. Feeding a high-fat diet causes activation of the JNK1 signaling pathway, insulin resistance, and obesity in mice. Germ-line ablation of Jnk1 prevents both diet-induced obesity and insulin resistance. Genetic analysis indicates that the effects of JNK1 on insulin resistance can be separated from effects of JNK1 on obesity. Emerging research indicates that JNK1 plays multiple roles in the regulation of insulin resistance, including altered gene expression, hormone/cytokine production, and lipid metabolism. Together, these studies establish JNK1 as a potential pharmacological target for the development of drugs that might be useful for the treatment of insulin resistance, metabolic syndrome, and type 2 diabetes.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Sabio
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D004032:Diet; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism
chemical_list: D048055:Mitogen-Activated Protein Kinase 8
references.citation: Science. 2008 Dec 5;322(5907):1483-4
references.pmid: 19056968
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3545-50
references.pmid: 18296638
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10741-6
references.pmid: 16818881
references.citation: Endocrinology. 2005 Oct;146(10):4410-6
references.pmid: 16020478
references.citation: Obesity (Silver Spring). 2010 Sep;18(9):1701-9
references.pmid: 20094041
references.citation: Nature. 2006 Dec 14;444(7121):860-7
references.pmid: 17167474
references.citation: Diabetes. 2003 Nov;52(11):2784-9
references.pmid: 14578297
references.citation: Cell Metab. 2006 Apr;3(4):267-75
references.pmid: 16581004
references.citation: Curr Opin Cell Biol. 2007 Apr;19(2):142-9
references.pmid: 17303404
references.citation: Cell Metab. 2008 May;7(5):421-33
references.pmid: 18460333
references.citation: Nature. 2001 Dec 13;414(6865):782-7
references.pmid: 11742409
references.citation: Cell. 2010 Mar 19;140(6):900-17
references.pmid: 20303879
references.citation: Cell. 2010 Feb 5;140(3):338-48
references.pmid: 20144759
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):6028-33
references.pmid: 20231445
references.citation: Cell. 2009 Jan 23;136(2):249-60
references.pmid: 19167327
references.citation: J Biol Chem. 2001 Jul 13;276(28):25889-93
references.pmid: 11342531
references.citation: Diabetes. 2009 Jan;58(1):116-24
references.pmid: 18952837
references.citation: Endocrinology. 2005 Aug;146(8):3417-27
references.pmid: 15845623
references.citation: J Biol Chem. 2000 May 26;275(21):15985-91
references.pmid: 10821852
references.citation: Science. 2008 Dec 5;322(5907):1539-43
references.pmid: 19056984
references.citation: J Biol Chem. 2005 Oct 21;280(42):35361-71
references.pmid: 16085647
references.citation: Endocrinology. 2007 Oct;148(10):4895-905
references.pmid: 17640984
references.citation: Diabetes. 2007 Aug;56(8):1986-98
references.pmid: 17519423
references.citation: Nature. 1997 Oct 9;389(6651):610-4
references.pmid: 9335502
references.citation: Kidney Int. 2009 Feb;75(4):381-8
references.pmid: 18971923
references.citation: Eur Cytokine Netw. 2006 Mar;17(1):4-12
references.pmid: 16613757
references.citation: J Biol Chem. 2007 Aug 3;282(31):22765-74
references.pmid: 17550900
references.citation: J Clin Invest. 2006 Nov;116(11):3015-25
references.pmid: 17053832
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16809-13
references.pmid: 18922779
references.citation: J Biol Chem. 2003 Jan 31;278(5):2896-902
references.pmid: 12417588
references.citation: J Appl Physiol (1985). 2007 Feb;102(2):816-8; discussion 818-9
references.pmid: 17284655
references.citation: Cell Metab. 2008 Jun;7(6):485-95
references.pmid: 18522830
references.citation: Antioxid Redox Signal. 2007 Mar;9(3):355-66
references.pmid: 17184181
references.citation: J Biol Chem. 2002 Jan 11;277(2):1531-7
references.pmid: 11606564
references.citation: Cell Metab. 2007 Nov;6(5):386-97
references.pmid: 17983584
references.citation: J Biol Chem. 2000 Mar 24;275(12):9047-54
references.pmid: 10722755
references.citation: Nat Med. 2004 Oct;10(10):1128-32
references.pmid: 15448687
references.citation: Diabetes. 1997 Jan;46(1):3-10
references.pmid: 8971073
references.citation: J Biol Chem. 2001 Dec 21;276(51):47944-9
references.pmid: 11604392
references.citation: Mol Cell Biol. 2010 Jan;30(1):106-15
references.pmid: 19841069
references.citation: Drug News Perspect. 2004 Sep;17(7):447-53
references.pmid: 15514704
references.citation: Diabetes. 2004 Apr;53(4):1060-7
references.pmid: 15047622
references.citation: Genes Dev. 2010 Feb 1;24(3):256-64
references.pmid: 20080940
references.citation: Genes Dev. 2001 Jun 1;15(11):1419-26
references.pmid: 11390361
references.citation: Curr Opin Pharmacol. 2003 Aug;3(4):420-5
references.pmid: 12901952
references.citation: J Biol Chem. 2002 Nov 1;277(44):42394-8
references.pmid: 12228220
references.citation: Diabetes. 2008 Oct;57(10):2644-51
references.pmid: 18633112
references.citation: J Clin Invest. 2006 Jul;116(7):1793-801
references.pmid: 16823477
references.citation: PLoS One. 2008 Sep 05;3(9):e3151
references.pmid: 18773087
references.citation: Genes Cells. 2007 Feb;12(2):143-54
references.pmid: 17295835
references.citation: J Appl Physiol (1985). 2007 Feb;102(2):814-6
references.pmid: 17068210
references.citation: Diabetes. 2007 Jun;56(6):1508-16
references.pmid: 17360977
references.citation: Diabetologia. 2008 Aug;51(8):1493-504
references.pmid: 18528680
references.citation: Nature. 2007 Jun 28;447(7148):1116-20
references.pmid: 17515919
references.citation: Physiol Rev. 2007 Apr;87(2):507-20
references.pmid: 17429039
references.citation: Cell Metab. 2009 Dec;10(6):491-8
references.pmid: 19945406
references.citation: Mol Cell. 2007 Aug 3;27(3):498-508
references.pmid: 17679097
references.citation: Biochem Biophys Res Commun. 2009 Jan 23;378(4):772-6
references.pmid: 19063863
references.citation: Nature. 2002 Nov 21;420(6913):333-6
references.pmid: 12447443
references.citation: Curr Opin Pharmacol. 2009 Dec;9(6):753-62
references.pmid: 19683471
references.citation: Mol Endocrinol. 2007 Sep;21(9):2294-302
references.pmid: 17579213
references.citation: Obesity (Silver Spring). 2008 Dec;16 Suppl 3:S11-22
references.pmid: 19190620
references.citation: Genes Dev. 2004 Aug 15;18(16):1976-80
references.pmid: 15314024
references.citation: Nat Med. 2002 Jan;8(1):75-9
references.pmid: 11786910
references.citation: J Biol Chem. 2004 Oct 29;279(44):45803-9
references.pmid: 15331609
references.citation: Cell. 2000 Oct 13;103(2):239-52
references.pmid: 11057897
references.citation: Science. 2003 Dec 5;302(5651):1710-1
references.pmid: 14657487
references.citation: Int J Obes (Lond). 2008 Dec;32 Suppl 7:S52-4
references.pmid: 19136991
references.citation: J Biol Chem. 2003 Apr 18;278(16):13740-6
references.pmid: 12560330
references.citation: Cell Metab. 2010 Jan;11(1):84-92
references.pmid: 20074531