组织特异性胰岛素抵抗及其代谢综合症的机制探讨.docVIP

组织特异性胰岛素抵抗及其代谢综合症的机制探讨 郭绍东 美国德克萨斯农工大学医学院医学系 通讯作者?: Shaodong Guo Division of Molecular Cardiology Department of Medicine College of Medicine Texas AM University Health Science Center 1901 South 1st Street, Bldg. 205 Temple, TX 76504, USA Tel: 254-743-1222 Fax: 254-743-0165 （USA) Email: sguo@medicine.tamhsc.edu Tissue-specific Insulin Resistance and Associated Mechanisms for the Metabolic Syndrome Shaodong Guo Abstract Metabolic syndrome is known as insulin resistance syndrome and has become a major public health problem worldwide. It is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia, and hypertension. Metabolic syndrome is a high risk factor for type 2 diabetes mellitus and cardiovascular diseases. As the most important hormone in the body in control of energy homeostasis, insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPK) and phosphotidylinositide-3-kinase (PI3K), of which activation of PI-3K-associated with insulin receptor substrate-1 and -2 (IRS1, 2) and subsequent Akt→Foxo1 phosphorylation cascade has a central role in control of nutrient homeostasis and organ survival. Inactivation of Akt and activation of Foxo1, through suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and over nutrition may provide the underlying mechanisms for metabolic syndrome. Targeting the IRS→Akt→Foxo1 signaling cascade will likely provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications in humans. This review discusses how a deficiency of insulin signaling components in different organs contributes to the feature of the metabolic syndrome. Emphasis will be placed on the role of IRS1, IRS2, and associated signaling pathways that couple to Akt and the forkhead/winged helix transcription factor Foxo1. Key words: Insulin r