title: c-Jun N-terminal kinase pathways in diabetes.
abstract: Type 2 diabetes develops from insulin resistance and has become a worldwide epidemic. The c-Jun N-terminal kinases have been considered as signaling molecules linking inflammation and insulin resistance. Genetic disruption of c-Jun N-terminal kinase-1 gene prevents the development of insulin resistance in obese and diabetic mice. Inhibition of c-Jun N-terminal kinases by a small cell-permeable peptide improves insulin sensitivity in mice. Hepatic inhibition of c-Jun N-terminal kinases using a dominant-negative protein or knockdown of c-Jun N-terminal kinase-1 gene by RNA interference reduces blood glucose and insulin levels and enhances hepatic insulin signaling in mice. Recent evidence demonstrates that the hepatic c-Jun N-terminal kinase pathway plays an important role in lipid and lipoprotein homeostasis in mice. This review discusses recent advances in our understanding of the role of c-Jun N-terminal kinase pathway in metabolic control and its potential as a target for the treatment of type 2 diabetes.
authors.affiliation: Merck & Co. Inc., Metabolic Disorders, Rahway, NJ 07065, United States. ruojing_yang@merck.com
authors.forename: Ruojing
authors.initials: R
authors.lastname: Yang
authors.forename: James M
authors.initials: JM
authors.lastname: Trevillyan
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008954:Models, Biological
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases