Diabetes research on models comprising intact animal tissues, cell cultures and isolated pancreatic islets is essential for understanding the pathogenesis of the disease as well as the mechanisms responsible for the chronic complications associated with it. Enormous advances in the understanding of the development of diabetes and its prevention have recently been derived from work with such animal models. This book presents the state-of-the-art knowledge in the field of diabetes research directed at understanding the mechanisms governing the development of skeletal muscle insulin resistance. Muscle Metabolism will be of significant interest for those researching diabetes at an experimental level in both academia and the pharmaceutical industry. In addition, it will also be of interest to researchers in the fields of obesity, metabolism, endocrinology and molecular biology.
Insulin Signaling. Overview: Tyrosine Kinase Signaling in Insulin Action. Defects in Early Insulin Signaling in Skeletal Muscle. Defects in Intermediate Insulin Signaling in Skeletal Muscle: (PI) 3-kinase and Glucose Transport. Glucose Transport. Glucose Transport in Muscle. The GLUT4 Compartments of Skeletal Muscle. Substrate Utilization. Adverse Metabolic Consequences of Hyperglycemia ("Glucose Toxicity"): Implications for the Pathogenesis of Diabetes Mellitus. Cellular Mediators of Glucose-Induced Autoregulation of Hexose Transport. Physiological Adaptations in Glucose Utilization of Skeletal Muscle. Fatty Acids and Muscle Insulin Resistance. Role of AMP Kinase and Malonyl CoA in Exercise-stimulated Skeletal Muscle Metabolism and Insulin Action. Transgenic and Genetic Models. The Use of Mouse Transgenic and Homologous Recombination Technologies to Analyze the Physiologic Basis of Glucose Homeostasis. Transgenic Approaches to Insulin Signaling. Transgenic Models to Study Glucose Transport and Metabolism in Skeletal Muscle. Diabetic Animals. Insulin Resistance in Skeletal Muscle: a Role for Impaired Insulin Activation of Glycogen Synthase. Muscle GLUT4 Traffic and Insulin Resistant States. Glucose Transport in Heart: Special Emphasis on Insulin Resistance and NIDM. Cellular Redox State and Insulin Sensitivity: Potential Role of Lipoic Acid. Exercise and Aging. Exercise Training and Muscle Insulin Resistance: Cellular Adaptations. Effects of Physical Exercise on the Decreased Insulin Action Caused by Aging. Effects of Aging on Glucose Homeostasis: Cellular Approaches. Application to Humans. Insulin Resistance: Whole Body Mechanisms in Humans. Cellular Mechanisms.