1;Preface;6 2;Contents;10 3;Contributors;12 4;Targeting Type 2 Diabetes;16 4.1;1 Inflamed About Obesity: Adipose Tissue and Insulin Resistance;17 4.2;2 The Lipotoxicity Concept;22 4.3;3 beta-Cell Failure: Link to Hyperglycaemia and T2DM;25 4.4;4 Role of the CNS in Glucose Homeostasis;27 4.5;5 Nutrient-Sensing Pathways in Calorie Restriction;29 4.6;6 Current Therapy;30 4.6.1;6.1 Published Algorithms;30 4.6.2;6.2 Metformin;31 4.6.3;6.3 Thiazolidinediones;32 4.6.4;6.4 GLP-1 Agonists and DPP-4 Inhibitors;33 4.7;7 Conclusions;34 4.8;References;35 5;Dual Acting and Pan-PPAR Activators as Potential Anti-diabetic Therapies;49 5.1;1 Introduction;50 5.2;2 PPAR-gamma;51 5.3;3 PPAR-a;52 5.4;4 PPAR-delta;53 5.5;5 Logic for Dual and Triple PPAR Activators in the Treatment of Diabetes and Insulin Resistance;53 5.6;6 The Bezafibrate Experience;54 5.7;7 Use of Combined Therapy with Fenofibrate and Glitazones;55 5.8;8 Dual PPAR-a/gamma Activator Drugs;56 5.9;9 Outlook for Dual PPAR-a/gamma Activators;58 5.10;10 PPAR-Pan Activators and PPAR-delta Dual Activators;59 5.11;11 Cancer Liability of PPAR Activators;60 5.12;12 Concluding Remarks;60 5.13;References;61 6;GLP-1 Agonists and Dipeptidyl-Peptidase IV Inhibitors;66 6.1;1 Type 2 Diabetes, Its Epidemiology, and the Need for Further Treatment Options;67 6.2;2 Incretin Hormones;67 6.2.1;2.1 GLP-1 Actions;69 6.2.2;2.2 Dipeptidyl-Peptidase IV;70 6.3;3 GLP-1 Receptor Agonists;71 6.3.1;3.1 Exenatide;72 6.3.2;3.2 Liraglutide;74 6.4;4 DPP-4 Inhibitors;75 6.4.1;4.1 Sitagliptin;76 6.4.2;4.2 Vildagliptin;77 6.4.3;4.3 Saxagliptin;77 6.5;5 Incretin-Based Therapies: Common Characteristics and Differences;78 6.6;6 Indications for Incretin-Based Therapies and Their Placement in Treatment Guidelines for Type 2 Diabetes;79 6.7;7 Incretin-Based Therapies and Type 1 Diabetes;81 6.8;References;82 7;Cannabinoids and Endocannabinoids in Metabolic Disorders with Focus on Diabetes;88 7.1;1 A Brief Introduction to the Endocannabinoid System;89 7.2;2 Central Endocannabinoid Control of Energy Balance;91 7.3;3 Peripheral Endocannabinoid Control of Energy Balance;95 7.4;4 Regulation and Dysregulation of the Endocannabinoid System in the Control of Metabolism;97 7.4.1;4.1 Role of Dysregulated Endocannabinoid Signaling in Type 2 Diabetes and Obesity-Related Metabolic and Cardiovascular Disorders;101 7.4.2;4.2 Endocannabinoid Dysregulation in Human Abdominal Obesity and Hyperglycemia: Relationship with Cardiometabolic Risk Factors and Type 2 Diabetes;105 7.5;5 Clinical Use of CB1 Receptor Antagonists/Inverse Agonists Against Type 2 Diabetes;106 7.6;6 Plant Cannabinoids and Type 1 Diabetes;109 7.6.1;6.1 Type 1 Diabetes Mellitus;109 7.7;7 Concluding Remarks;110 7.8;References;111 8;SGLT Inhibitors as New Therapeutic Tools in the Treatment of Diabetes;118 8.1;1 Preface;119 8.2;2 The Sodium-d-Glucose Cotransporter as Target;119 8.2.1;2.1 Role of Sodium-d-Glucose Cotransport in Transepithelial Sugar Transport;119 8.2.2;2.2 Molecular Basis of Sodium-d-Glucose Cotransport;121 8.2.3;2.3 Sugar Binding Sites of the SGLT;122 8.2.3.1;2.3.1 Substrate Specificity of the Sodium-d-Glucose Cotransporters;122 8.2.3.2;2.3.2 Sugar Binding Site(s) of the Sodium-d-Glucose Cotransporter;124 8.3;3 The Prototype of SGLT Inhibitors: Phlorizin;124 8.3.1;3.1 General Remarks;124 8.3.2;3.2 SGLT as Phlorizin Receptor;125 8.3.2.1;3.2.1 Binding Studies on Brush Border Membranes;125 8.3.2.2;3.2.2 Interactions of Phlorizin with the Isolated Transporter and Its Subdomains;125 8.3.2.3;3.2.3 Differences Between hSGLT1 and hSGLT2;126 8.3.3;3.3 Pharmacophore Analysis and Dimensions of the Phlorizin Binding Pocket;126 8.4;4 Synthesis and Screening of Derivates of Phlorizin;127 8.4.1;4.1 O-glucosides, C-arylglucosides, N-glucosides and S-glycosides;127 8.4.2;4.2 Screening Methods;129 8.4.2.1;4.2.1 Cellular Assays;129 8.4.2.2;4.2.2 Animal Models;130 8.5;5 Therapeutic Efficacy of SGLT Inhibitors;130 8.5.1;5.1 In Vitro Studies on Sugar Transport by Cultured Transfected Ce