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Determination of Insulin Signaling Pathways in Hepatocytes  

Kim, Sang-Kyum (College of Pharmacy and Research Center for Transgenic Cloned Pigs, Chungnam National University)
Publication Information
Toxicological Research / v.21, no.3, 2005 , pp. 195-208 More about this Journal
Abstract
Diabetes is a major cause of morbidity and mortality, and associated with a high risk of atherosclerosis, and liver, kidney, nerve and tissue damage. Defective insulin secretion in pancreas and/or insulin resistance in peripheral tissues is a central component of diabetes. It is well established that, regardless of the degree of muscle insulin resistance, glucose levels in diabetic and non-diabetic individuals are determined by the rate of hepatic glucose production. Moreover recently studies using liver-specific insulin receptor knockout mice show the paramount role of the liver in insulin resistance and diabetes. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. The first major section of this review defines the major insulin-mediated signaling pathways including phosphatidylinositol 3-kinase and mitogen activated protein kinases. The second major section of the review presents a summary and evaluation of methods for determination of the role and function of signaling pathways, including methods for determination of kinase phosphorylation, the use of pharmacological inhibitors of kinase and dominant-negative kinase constructs, and the application of new RNA interference methods.
Keywords
Insulin signaling; Diabetes; Insulin resistance; Protein kinase; RNA interference; Dominant negative construct;
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