Understanding Insulin Action: Principles and Molecular Mechanisms

ISBN-13: 9781461287940 / Angielski / Miękka / 2011 / 129 str.

J. Espinal

Opis

Every year between three and four hundred papers are published on the topic of insulin action. This extraordinary publication rate prevents any author from includ- ing an exhaustive bibliography in any review or book. Perhaps due to this there is no single text that attempts to cover the effects and the mechanism of action of insulin. This book is such an attempt. I intend to present a review of the physiological effects of insulin, the pathology of defects in the action of insulin, and the current views on the mechanism of action of this hormone. I make no apology for the fact that the bibliography will not be extensive and that the amount of experimental detail and data discussed will be kept to a relevant minimum. This book is not intended for the expert in the field, but for the second- or third-year undergraduate and graduate student of medicine, biochemistry, physiology or related disciplines, and will be valuable as a reference source for research workers. The book is presented as a guide, a summary of the ideas and facts; it will present a reader with a foretaste of a fascinating and ever-changing field. I have attempted to be up-to-date with published research work. Any significant contributions to the field not included in the first draft have been added as footnotes. I assume a basic knowledge of the metabolic pathways of carbohydrates, fats and proteins.

Spis treści

1 Introduction.- 1.1 A short account of the discovery of insulin.- 1.2 An overview of insulin action and diabetes.- 2 Insulin: Chemistry, Synthesis and Secretion.- 2.1 The insulin molecule.- 2.1.1 Primary structure and evolutionary conservation.- 2.1.2 X-ray analysis and structure-activity relationships.- 2.2 Insulin synthesis.- 2.2.1 The insulin gene.- 2.2.2 Regulation of insulin gene expression.- 2.2.3 Physiological regulation of gene expression.- 2.2.4 Pathology of insulin gene expression.- 2.3 Insulin secretion.- 2.3.1 Morphology of the islets of Langerhans.- 2.3.2 Glucose metabolism in the P-cell.- 2.3.3 Role of Ca2+ in insulin secretion.- 2.3.4 Role of cAMP in insulin secretion.- 3 Pathophysiology of Insulin.- 3.1 Introduction.- 3.2 Metabolic effects of insulin.- 3.2.1 Effects on carbohydrate metabolism.- 3.2.2 Effects on fat metabolism.- 3.2.3 Effects on protein metabolism.- 3.2.4 Summary.- 3.3 Diabetes.- 3.3.1 Insulin-dependent diabetes mellitus (IDDM).- 3.3.2 Non-insulin-dependent diabetes mellitus (NIDDM).- 4 Molecular Mechanisms Involved in Insulin Action.- 4.1 Regulation of protein phosphorylation.- 4.1.1 Insulin-stimulated increases in protein phosphorylation.- 4.1.2 Insulin-stimulated decreases in protein phosphorylation.- 4.2 Insulin regulation of protein traffic.- 4.2.1 Insulin stimulation of glucose transport.- 4.2.2 Translocation of IGF-II receptors and other proteins.- 4.3 Regulation of gene expression.- 4.3.1 Effects of insulin on phosphoenolpyruvate carboxyl-kinase (PEPCK) gene expression.- 4.3.2 Effects of insulin on glyceraldehyde phosphate dehydrogenasel (GAPDH) mRNA.- 5 The Insulin Receptor.- 5.1 Receptor structure.- 5.1.1 Methods used in determining the structure of the insulin receptor.- 5.1.2 Subunit composition.- 5.1.3 The insulin receptor precursor and its gene.- 5.1.4 Relationship to other receptors.- 5.2 The insulin receptor tyrosine kinase.- 5.2.1 Phosphorylation of the insulin receptor.- 5.2.2 Substrates for the insulin receptor tyrosine kinase.- 5.2.3 Physiological role of insulin receptor tyrosine kinase phosphorylation.- 5.3 Insulin receptor internalization.- 6 Molecular Mechanisms of Insulin Signal Transduction.- 6.1 The cAMP system.- 6.1.1 Effects of insulin on the cAMP system.- 6.2 The inositoltrisphosphate-diacylglycerol system.- 6.2.1 Inositol lipid metabolism.- 6.2.2 Mechanism of second-messenger action.- 6.2.3 Summary of the hypothesis.- 6.2.4 Insulin action and the Insl,4,5P3/DG system.- 6.3 The involvement of glycosylphosphatidylinositol (GPI) in insulin action.- 6.3.1 Anchoring of membrane proteins by GPIs.- 6.3.2 GPI in insulin action.- 7 Summary and Perspectives.- 7.1 Summary.- 7.2 Perspectives.