Chapter 10 How Insulin Regulates Glucose Transport in Adipocytes

Insulin stimulates glucose storage and metabolism by the tissues of the body, predominantly liver, muscle and fat. Storage in muscle and fat is controlled to a large extent by the rate of facilitative glucose transport across the plasma membrane of the muscle and fat cells. Insulin controls this transport. Exactly how remains debated. Work presented in this review focuses on the pathways responsible for the regulation of glucose transport by insulin. We present some historical work to show how the prevailing model for regulation of glucose transport by insulin was originally developed, then some more recent data challenging this model. We finish describing a unifying model for the control of glucose transport, and some very recent data illustrating potential molecular machinery underlying this regulation. This review is meant to give an overview of our current understanding of the regulation of glucose transport through the regulation of the trafficking of Glut4, highlighting important questions that remain to be answered. A more detailed treatment of specific aspects of this pathway can be found in several excellent recent reviews (Brozinick et al., 2007 Hou and Pessin, 2007; Huang and Czech, 2007;Larance et al., 2008 Sakamoto and Holman, 2008; Watson and Pessin, 2007; Zaid et al., 2008)One of the main objectives of this review is to discuss the results of the experiments measuring the kinetics of Glut4 movement between subcellular compartments in the context of our emerging model of the Glut4 trafficking pathway.