Prevention of fat-induced insulin resistance by salicylate. Export

@article{citeulike:264030, abstract = {Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-beta. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-beta. Whole-body glucose uptake and metabolism were estimated using [3-(3)H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-(14)C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1-associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-beta. Unlike the response in wild-type mice, IKK-beta knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.}, address = {Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA.}, author = {Kim, J. K. and Kim, Y. J. and Fillmore, J. J. and Chen, Y. and Moore, I. and Lee, J. and Yuan, M. and Li, Z. W. and Karin, M. and Perret, P. and Shoelson, S. E. and Shulman, G. I.}, citeulike-article-id = {264030}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11489937}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11489937}, issn = {0021-9738}, journal = {J Clin Invest}, keywords = {aspirin, fat, fattyacids, insulinresistance, nfkb}, month = {August}, number = {3}, pages = {437--446}, posted-at = {2005-07-25 08:47:56}, priority = {2}, title = {Prevention of fat-induced insulin resistance by salicylate.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11489937}, volume = {108}, year = {2001} }

TY - JOUR ID - citeulike:264030 L3 - citeulike-article-id:264030 N2 - Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-beta. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-beta. Whole-body glucose uptake and metabolism were estimated using [3-(3)H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-(14)C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1-associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-beta. Unlike the response in wild-type mice, IKK-beta knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes. IS - 3 JF - J Clin Invest SN - 0021-9738 AD - Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-8012, USA. EP - 446 TI - Prevention of fat-induced insulin resistance by salicylate. VL - 108 SP - 437 KW - aspirin KW - fat KW - fattyacids KW - insulinresistance KW - nfkb AU - Kim, JK AU - Kim, YJ AU - Fillmore, JJ AU - Chen, Y AU - Moore, I AU - Lee, J AU - Yuan, M AU - Li, ZW AU - Karin, M AU - Perret, P AU - Shoelson, SE AU - Shulman, GI PY - 2001/08// UR - http://view.ncbi.nlm.nih.gov/pubmed/11489937 ER -