Metabolic Syndrome : Underlying Mechanisms and Drug Therapies

This book provides a comprehensive overview of the development of metabolic syndrome, the underlying mechanisms and therapeutic strategies for drug development. The authors examine the context of underlying molecular pathways and integrated physiology, then expanding the discussion to diseases associated with metabolic syndrome. The development of drug therapies for these diseases and complications is extensively covered. The book offers a comprehensive and in-depth view of energy metabolism, metabolic tissues and pathways, molecular mechanism-based drug discovery and clinical implications. Metabolic Syndrome: Underlying Mechanisms and Drug Therapies......Page 5 Contents......Page 7 Introduction......Page 11 Contributors......Page 13 Part One: The Physiology of Metabolic Tissues Under Normal and Disease States......Page 17 1: Gut as an Endocrine Organ: the Role of Nutrient Sensing in Energy Metabolism......Page 19 2: Central Glucose Sensing and Control of Food Intake and Energy Homeostasis......Page 45 3: Abnormalities in Insulin Secretion in Type 2 Diabetes Mellitus......Page 69 4: Adipokine Production by Adipose Tissue: A Novel Target for Treating Metabolic Syndrome and its Sequelae......Page 89 5: Hepatic Metabolic Dysfunctions in Type 2 Diabetes: Insulin Resistance and Impaired Glucose Production and Lipid Synthesis......Page 149 6: Energy Metabolism in Skeletal Muscle and its Link to Insulin Resistance......Page 173 Part Two: Metabolic Diseases and Current Therapies......Page 193 7: Mechanisms and Complications of Metabolic Syndrome......Page 195 8: Emerging Therapeutic Approaches for Dyslipidemias Associated with High LDL and Low HDL......Page 215 9: Mechanism of Action of Niacin: Implications for Atherosclerosis and Drug Discovery......Page 251 10: Current Antidiabetic Therapies and Mechanisms......Page 269 Part Three: Drug Targets for Antidiabetic Therapies......Page 295 11: GLP-1 Biology, Signaling Mechanisms, Physiology, and Clinical Studies......Page 297 12: Dipeptidyl Peptidase IV Inhibitors for Treatment of Diabetes......Page 343 13: Sodium Glucose Cotransporter 2 Inhibitors......Page 375 14: Fibroblast Growth Factor 21 as a Novel Metabolic Regulator......Page 393 15: Sirtuins as Potential Drug Targets for Metabolic Diseases......Page 407 16: 11β-Hydroxysteroid Dehydrogenase Type 1 as a Therapeutic Target for Type 2 Diabetes......Page 439 17: Monoclonal Antibodies for the Treatment of Type 2 Diabetes: A Case Study with Glucagon Receptor Blockade......Page 475 Part Four: Lessons Learned and Future Outlook......Page 485 18: Drug Development for Metabolic Diseases: Past, Present, and Future......Page 487 Index......Page 505 Gut as an endocrine organ : the role of nutrient-sensing in energy metabolism / Minghan Wang Central glucose sensing and control of food intake and energy homeostasis / Lourdes Mounien and Bernard Thorens Abnormalities in insulin secretion in type 2 diabetes mellitus / Taly Meas and Pierre-Jean Guillausseau Adipokine production by adipose tissue : a novel target for treating metabolic syndrome and its sequelae / Vanessa DeClercq ... [et al.] Hepatic metabolic dysfunctions in type 2 diabetes : insulin resistance and impaired glucose production and lipid synthesis / Ruojing Yang Energy metabolism in skeletal muscle and its link to insulin resistance / Minghan Wang Mechanisms and complications of metabolic syndrome / Minghan Wang Emerging therapeutic approaches for dyslipidemias associated with high LDL and low HDL / Margrit Schwarz and Jae B. Kim Mechanism of action of niacin : implications for atherosclerosis and drug discovery / Devan Marar ... [et al.] Current antidiabetic therapies and mechanisms / Minghan Wang GLP-1 biology, signaling mechanisms, physiology, and clinical studies / Remy Burcelin ... [et al.] Dipeptidyl peptidase IV inhibitors for treatment of diabetes / McIntosh, C.H.S. ... [et al.] Sodium glucose co-transporter 2 inhibitors / Margaret Ryan and Serge A. Jabbour Fibroblast growth factor 21 as a novel metabolic regulator / Radmila Micanovic, James D. Dunbar, and Alexei Kharitonenkov Sirtuins as potential drug targets for metabolic diseases / Qiang Tong 11-hydroxysteroid dehydrogenase type 1 as a therapeutic target for type 2 diabetes / Clarence Hale and David J. St. Jean, Jr Monoclonal antibodies for the treatment of type 2 diabetes : a case study with glucagon receptor blockade / Hai Yan, Wei Gu, and Murielle Veniant-Ellison Drug development for metabolic diseases: past, present and future / Minghan Wang. METABOLIC SYNDROME A comprehensive look at the fight against the metabolic syndrome epidemic Increasing risk of cardiovascular disease and diabetes, the metabolic syndrome is a world health problem that demands attention from all levels of the health care industry. Metabolic Syndrome: Underlying Mechanisms and Drug therapies extensively covers the metabolic syndrome with an emphasis on drug discovery efforts, providing a context of molecular mechanisms and drug pharmacology for pharmaceutical scientists. The book starts by examining the physiology of metabolic tissues under normal and disease states, followed by discussions of metabolic diseases and clinical complications. The development of drug therapies based on emerging science is then covered extensively. In addition, there is an in-depth look into the metabolic pathways and dysfunctions in metabolic disease, especially type 2 diabetes and lipid disorders. Finally, a chapter is devoted to past successes and failures in metabolic drug discovery as well as an outlook on future development and challenges. Divided into four parts, the book: Addresses important metabolic syndrome basics at the psychological level and metabolic abnormalities at the tissue and pathway levels Covers the identification of pathways and molecular targets for the development of anti-diabetic therapies Details pharmaceutical industry approach to solving metabolic and obesity related problems Describes drug therapies and their limitations and complications, offering a “lessons learned” from existing treatments With a clear organization and extensive collection of references, the book is a user-friendly and unique tool for scientists in a variety of scientific disciplines in the pharmaceutical and biotechnology industries. A comprehensive resource, this book offers an overview of the development of metabolic syndrome, the underlying mechanisms and therapeutic strategies for drug development. The authors examine the context of underlying molecular pathways and integrated physiology, then expanding the discussion to diseases associated with metabolic syndrome. Coverage in this book encompasses the physiology of metabolic tissues under normal and disease states; mechanisms, complications, and current therapies; and drug targets for antidiabetic therapies