Hansen / Bray The Metabolic Syndrome:

Epidemiology, Clinical Treatment, and Underlying Mechanisms
1. Auflage 2010
ISBN: 978-1-60327-116-5
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 402 Seiten, Web PDF

Reihe: Medicine (R0)

With an extraordinary need for early intervention and prevention to slow or halt its progression, metabolic syndrome is one of the most challenging health problems. Only through an understanding of the science underlying this syndrome can successful interventions be developed and implemented.

This book covers the most important clinical and bench science aspects of metabolic syndrome. Coverage includes updated clinical views on the syndrome, its definition, current and future treatment options, and a critical evaluation of the current status of each of the syndrome components, including the latest knowledge of casual mechanisms.

The writers stimulate new thinking concerning the underlying mechanisms and encourage heightened efforts to develop new therapeutics, potentially targeting uniquely intersecting pathways.

Zielgruppe

Professional/practitioner

Autoren/Hrsg.

Hansen, Barbara C.

Bray, George A.

Inhaltsverzeichnis

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.

Leseproben

"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)."