Metabolic Syndrome

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.

Introduction ix Minghan Wang Contributors xi Part One The Physiology of Metabolic Tissues Under Normal and Disease States 1. Gut as an Endocrine Organ: the Role of Nutrient Sensing in Energy Metabolism 3 Minghan Wang 2. Central Glucose Sensing and Control of Food Intake and Energy Homeostasis 29 Lourdes Mounien and Bernard Thorens 3. Abnormalities in Insulin Secretion in Type 2 Diabetes Mellitus 53 Taly Meas and Pierre-Jean Guillausseau 4. Adipokine Production by Adipose Tissue: A Novel Target for Treating Metabolic Syndrome and its Sequelae 73 Vanessa DeClercq, Danielle Stringer, Ryan Hunt, Carla G. Taylor, and Peter Zahradka 5. Hepatic Metabolic Dysfunctions in Type 2 Diabetes: Insulin Resistance and Impaired Glucose Production and Lipid Synthesis 133 Ruojing Yang 6. Energy Metabolism in Skeletal Muscle and its Link to Insulin Resistance 157 Minghan Wang Part Two Metabolic Diseases and Current Therapies 7. Mechanisms and Complications of Metabolic Syndrome 179 Minghan Wang 8. Emerging Therapeutic Approaches for Dyslipidemias Associated with High LDL and Low HDL 199 Margrit Schwarz and Jae B. Kim 9. Mechanism of Action of Niacin: Implications for Atherosclerosis and Drug Discovery 235 Devan Marar, Shobha H. Ganji, Vaijinath S. Kamanna, and Moti L. Kashyap 10. Current Antidiabetic Therapies and Mechanisms 253 Minghan Wang Part Three Drug Targets for Antidiabetic Therapies 11. GLP-1 Biology, Signaling Mechanisms, Physiology, and Clinical Studies 281 Remy Burcelin, Cendrine Cabou, Christophe Magnan, and Pierre Gourdy 12. Dipeptidyl Peptidase IV Inhibitors for Treatment of Diabetes 327 C.H.S. McIntosh, S.-J. Kim, R.A. Pederson, U. Heiser, and H.-U. Demuth 13. Sodium Glucose Cotransporter 2 Inhibitors 359 Margaret Ryan and Serge A. Jabbour 14. Fibroblast Growth Factor 21 as a Novel Metabolic Regulator 377 Radmila Micanovic, James D. Dunbar, and Alexei Kharitonenkov 15. Sirtuins as Potential Drug Targets for Metabolic Diseases 391 Qiang Tong 16. 11β-Hydroxysteroid Dehydrogenase Type 1 as a Therapeutic Target for Type 2 Diabetes 423 Clarence Hale and David J. St. Jean, Jr. 17. Monoclonal Antibodies for the Treatment of Type 2 Diabetes: A Case Study with Glucagon Receptor Blockade 459 Hai Yan, Wei Gu, and Murielle Veniant-Ellison Part Four Lessons Learned and Future Outlook 18. Drug Development for Metabolic Diseases: Past, Present and Future 471 Minghan Wang Index 489