The Metabolic Syndrome:
Epidemiology, Clinical Treatment, and Underlying Mechanisms
1st Edition
Published on 6. May 2010
XII, 402 pages
978-1-60327-116-5 (ISBN)
Description
In the United States, 40 to 45% of those over 60 years of age have the metabolic syndrome (1,2,3), and this percentage, based on estimates of the increasing prevalence ofexcess body weight and the more comprehensive diagnostic criteria for the syndrome, is likely to exceed 60% in newer survey analyses. Children and adolescents, too, are being affected by the metabolic syndrome, in parallel with the increasing prevalence of overweight in young people, now estimated to include 16% of those age 6 to 19 years. Clinicians see with increasing frequency that routine office visits demonstrate the meta bolic syndrome, a constellation of discrete but closely related metabolic disturbances indicative of increased risk for (or presence of) cardiovascular disease and/or diabetes. All estimates suggest the increasing impactof the metabolic syndrome on mortality and morbidity (4). Our aim in developing this new synthesis and analysis of the metabolic syndrome has been to bring together the viewpoints of the epidemiologists, the physiologists, the molecular biologists/biochemists, and the clinicians toward understanding the current state ofknowledge ofboth the causes and the consequences of the metabolic syndrome. These writers aim to stimulate new thinking concerning underlying mechanisms and to encourage heightened efforts to develop new therapeutics, potentially targeting uniquely intersecting pathways or points of intervention. This book is an extended call to action to slow or halt the rising tide of the metabolic syndrome (5).
Reviews / Votes
From the reviews:
"This book presents a balanced view of the controversies surrounding the metabolic syndrome and supplies the reader with a detailed account of the key issues that divide the various camps. . is an admirable collection of scientifically focused and up-to-date views of the current thinking on the metabolic syndrome. It can be recommended for scientists working in this field as well as for clinicians who wish to gain a deeper understanding of this complex syndrome." (Arne Astrup, The New England Journal of Medicine, July, 2008)
"This book covers three major perspective of the metabolic syndrome . . this book is written for an endocrinology audience and anyone who has a strong interest in the link between the basic science of insulin resistance and the clinical manifestations of the metabolic syndrome. Practitioners will find useful information about the underlying mechanisms of the disease as well as an overview of treatment approaches. . This is a high quality review of insulin resistance targeted at endocrinologists and basic scientists." (Matthew J. Sorrentino, Doody's Review Service, November, 2008)
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Other editions
Additional editions
Barbara C. Hansen | George A. Bray
The Metabolic Syndrome:
Epidemiology, Clinical Treatment, and Underlying Mechanisms
Book
01/2008
Humana Press Inc.
€213.99
Shipment within 15-20 days
Content
Metabolic Syndrome-Past and Future.- Metabolic Syndrome-Past and Future.- Epidemilogy And Clinical Treatment: Issues In Defining And Treating The Metabolic Syndrome.- Metabolic Syndrome.- The Role of Obesity in Insulin Resistance.- Treatment of the Metabolic Syndrome with Weight Loss, Exercise, Hormones, and Surgery.- Insulin Resistance, Metabolic Syndrome, and Cardiovascular Disease.- The Sympatho-Adrenal System in the Metabolic Syndrome.- Endothelial Function, Inflammation, and Dyslipidemia.- Insulin Action and Endothelial Function.- Macro- and Microvascular Disease in an Insulin-Resistant Pre-Diabetic Animal Model.- High-Sensitivity C-Reactive Protein and the Metabolic Syndrome.- Insulin Signaling in Adipocytes and the Role of Inflammation.- Insulin Resistance and Dyslipidemia.- Insulin-Secretion and Action: Underlying Mechanisms of the Metabolic Syndrome.- Pancreatic Islet Pathophysiology and Pathology in Obesity.- Glucagon-like Peptides and Insulin Sensitivity.- The Relationship Between the Insulin Receptor Substrates and Metabolic Disease.- Insulin Resistance and Inhibitors of the Insulin Receptor Tyrosine Kinase.- Fat Feeding and Muscle Fat Deposition Eliciting Insulin Resistance.- Alterations in Atypical Protein Kinase C Activation in Insulin Resistance Syndromes.- The Liver, Glucose Homeostasis, and Insulin Action in Type 2 Diabetes Mellitus.- Chronomics of the Metabolic Syndrome.
"II ENDOTHELIAL FUNCTION, INFLAMMATION, AND DYSLIPIDEMIA (p. 107-108)
7 Insulin Action and Endothelial Function
INTRODUCTION
The endothelium is a diaphanous cellular monolayer lining the lumen of the vasculature throughout the body and weighs approximately 1.8 kg in a 70 kg man. In addition to its well-recognized passive barrier and transport functions, the endothelium actively participates in processes related to local vascular and tissue health. These include active control of vascular tone (1,2), regulation of blood fluidity (3), and modulation of monocyte adhesion (4,5), inflammation (6,7), and lipid peroxidation (8-10), to name but a few processes.
More recently, the endothelium has been recognized as an endocrine organ. Indeed, the endothelium produces a variety of hormones acting in a paracrine fashion to regulate vascular tone as well as growth and remodeling of the vascular wall (11-14). The endothelium also possesses receptors for humoral ligands. These receptors, whose predominant role was initially thought to be transendothelial transfer of hormones, are now known to directly activate signaling cascades and physiological responses.
This chapter discusses the evidence and functional implications of the endothelium as a target tissue for insulin action and the pathophysiological consequences of insulin resistance. We present evidence from in vitro and in vivo studies demonstrating that the vascular endothelium responds to insulin by increasing the release of nitric oxide (the dominant endothelium-derived vasodilator and anti-atherosclerotic factor), and that this action is impaired in states of insulin resistance.
More recent data implicating insulin and other metabolic factors in the regulation of endothelin (the primary endotheliumderived vasoconstrictor and pro-atherosclerotic agent) are also reviewed. Pathophysiological implications relevant to cardiovascular disease in insulin resistance and the opportunities for novel treatment approaches are discussed.
MOLECULAR MECHANISMS OF INSULIN SIGNALING IN THE VASCULATURE
Insulin Signaling Pathways Regulating Production ofNO One important biological action of insulin in vascular endothelium is to directly stimulate production of nitric oxide (NO), a potent vasodilator (15,16). Classical vasodilators such as acetylcholine bind and activate specific G-protein-coupled receptors on the surface of endothelial cells, leading to generation of inositol trisphosphate (lP3) and subsequent increases in intracellular Ca2+ levels.
Ca2+/calmodulin complexes bind to a specific region on eNOS that promotes dissociation of eNOS from caveolin-l and enhances activation of eNOS (Fig. 7.1) (17,18). Signaling pathways leading from the insulin receptor to activation of eNOS are distinct and separable from the classical signaling pathways linking G-protein-coupled receptors to eNOS (19). Studies of endothelial cells in primary culture have elucidated a complete biochemical signaling pathway leading from the insulin receptor to activation of eNOS (19-22)."
7 Insulin Action and Endothelial Function
INTRODUCTION
The endothelium is a diaphanous cellular monolayer lining the lumen of the vasculature throughout the body and weighs approximately 1.8 kg in a 70 kg man. In addition to its well-recognized passive barrier and transport functions, the endothelium actively participates in processes related to local vascular and tissue health. These include active control of vascular tone (1,2), regulation of blood fluidity (3), and modulation of monocyte adhesion (4,5), inflammation (6,7), and lipid peroxidation (8-10), to name but a few processes.
More recently, the endothelium has been recognized as an endocrine organ. Indeed, the endothelium produces a variety of hormones acting in a paracrine fashion to regulate vascular tone as well as growth and remodeling of the vascular wall (11-14). The endothelium also possesses receptors for humoral ligands. These receptors, whose predominant role was initially thought to be transendothelial transfer of hormones, are now known to directly activate signaling cascades and physiological responses.
This chapter discusses the evidence and functional implications of the endothelium as a target tissue for insulin action and the pathophysiological consequences of insulin resistance. We present evidence from in vitro and in vivo studies demonstrating that the vascular endothelium responds to insulin by increasing the release of nitric oxide (the dominant endothelium-derived vasodilator and anti-atherosclerotic factor), and that this action is impaired in states of insulin resistance.
More recent data implicating insulin and other metabolic factors in the regulation of endothelin (the primary endotheliumderived vasoconstrictor and pro-atherosclerotic agent) are also reviewed. Pathophysiological implications relevant to cardiovascular disease in insulin resistance and the opportunities for novel treatment approaches are discussed.
MOLECULAR MECHANISMS OF INSULIN SIGNALING IN THE VASCULATURE
Insulin Signaling Pathways Regulating Production ofNO One important biological action of insulin in vascular endothelium is to directly stimulate production of nitric oxide (NO), a potent vasodilator (15,16). Classical vasodilators such as acetylcholine bind and activate specific G-protein-coupled receptors on the surface of endothelial cells, leading to generation of inositol trisphosphate (lP3) and subsequent increases in intracellular Ca2+ levels.
Ca2+/calmodulin complexes bind to a specific region on eNOS that promotes dissociation of eNOS from caveolin-l and enhances activation of eNOS (Fig. 7.1) (17,18). Signaling pathways leading from the insulin receptor to activation of eNOS are distinct and separable from the classical signaling pathways linking G-protein-coupled receptors to eNOS (19). Studies of endothelial cells in primary culture have elucidated a complete biochemical signaling pathway leading from the insulin receptor to activation of eNOS (19-22)."
