Incretins and Insulin Secretion (eBook)

Front Cover 1
Vitamins and Hormones: Incretins and Insulin Secretion 4
Copyright 5
Former Editors 6
Contents 8
Contributors 14
Preface 18
Chapter 1: Evolution of Genes for Incretin Hormones and their Receptors 20
I. Introduction 21
II. Evolution on Incretin Hormone Genes 24
III. Evolution of Incretin Hormone Receptor Genes 31
IV. Evolution of Incretins 34
Acknowledgments 35
References 36
Chapter 2: Pleiotropic Actions of the Incretin Hormones 40
I. Introduction 41
II. GIP and GLP-1 Actions: Hormonal and Neuronal Pathways 43
III. Effects of GIP and GLP-1 on Early Events During Feeding 46
IV. Effects of Incretins on Functions of the Endocrine Pancreas 47
V. Effects of GLP-1 on Food Intake and Satiety 63
VI. Gastrointestinal Effects of GIP and GLP-1 65
VII. Cardiovascular Effects of GIP and GLP-1 67
VIII. Effects of GIP and GLP-1 on Nutrient Storage and Flux 70
IX. Effects of GIP and GLP-1 on Bone 73
X. The Future 74
Acknowledgments 75
References 75
Chapter 3: Dietary Effects on Incretin Hormone Secretion 100
I. Introduction 101
II. Physiology of the Incretin Hormones 101
III. Dietary Influence on Incretin Hormone Secretion 104
IV. Mechanisms by Which Nutrients Stimulate Incretin Release 111
V. Incretin Responses in Obesity and Diabetes 116
VI. Therapeutic Implications 117
VII. Conclusions 119
Acknowledgments 120
References 120
Chapter 4: K-cells and Glucose-Dependent Insulinotropic Polypeptide in Health and Disease 130
I. History of K-cells and GIP 131
II. The GIP Gene and Regulation of its Expression 134
III. Anatomical Localization and Development of K-cells 136
IV. Secretion, Degradation, and Elimination of GIP 139
V. Biological Actions of GIP 145
VI. GIP and K-cells in Health and Disease 147
VII. Clinical Application of GIP and K-cells 152
References 154
Chapter 5: The Emerging Role of Promiscuous 7TM Receptors as Chemosensors for Food Intake 170
I. Introduction 172
II. Family C Receptors as Promiscuous Sensors for l-a-Amino acids, Peptides, Divalent cations, and Carbohydrates... 172
III. Family A Receptors as Promiscuous Sensors for Peptone and Free Fatty Acids (FFAs) 183
IV. Therapeutic Perspectives 193
Acknowledgments 194
References 194
Chapter 6: Central Regulation of Glucose-Dependent Insulinotropic Polypeptide Secretion 204
I. Introduction 205
II. Structure and Action of GIP 205
III. Regulation of GIP Secretion 207
IV. Neural Regulation of GIP Secretion 207
V. The Role of Autonomic Nervous System 207
VI. Concluding Remarks 215
References 215
Chapter 7: Incretin Hormone Secretion Over the Day 222
I. Introduction 223
II. GIP and GLP-1 Secretion After Meal Ingestion 223
III. Regulation of GIP and GLP-1 Secretion 225
IV. Mechanisms of GIP and GLP-1 Secretion 228
V. GIP and GLP-1 Secretion Over the Day 228
VI. Incretin Hormone Secretion in Glucose Intolerance and Disease States 230
VII. GIP and GLP-1 Secretion in Fasting State 233
VIII. Conclusion and Perspective 234
Acknowledgments 235
References 235
Chapter 8: Using the Lymph Fistula Rat Model to Study Incretin Secretion 240
I. Introduction 241
II. The Incretin Hormones 242
III. Anatomy and Physiology of the Gastrointestinal and Lymphatic Systems 246
IV. The Lymph Fistula Model 248
V. Using the Lymph Fistula Rat Model to Study Incretin Secretion 251
VI. Concluding Remarks and Future Directions 261
Acknowledgments 263
References 263
Chapter 9: Structural Basis for Ligand Recognition of Incretin Receptors 270
I. G-Protein-Coupled Receptors 271
II. The GLP-1 Receptor 273
III. The GIP Receptor 286
IV. Common and Divergent Features of GLP-1R and GIPR Ligand Binding 290
References 293
Chapter 10: Epac2-Dependent Rap1 Activation and the Control of Islet Insulin Secretion by Glucagon-Like Peptide-1 298
I. Introduction 299
II. PKA and Epac2 Regulate Insulin Secretion from beta Cells 299
III. Epac2 Activates Rap1 GTPase 302
IV. Rap1 Effectors and Their Potential Roles in the Control of GSIS 304
V. Interactions of Epac2 with Secretory Granule-Associated Proteins 313
VI. Conclusions 315
Acknowledgments 316
References 316
Chapter 11: Central GLP-1 Actions on Energy Metabolism 322
I. Introduction 323
II. CNS Glucagon-Like Peptide 1 and Energy Intake 324
III. CNS Glucagon-Like Peptide 1 and Glucose Metabolism 327
IV. CNS Glucagon-Like Peptide 1 and Lipid Metabolism 329
V. Future Directions 330
Acknowledgments 332
References 332
Chapter 12: Glucagon-Like Peptide-1:... 338
I. Introduction 339
II. GLP-1 in Metabolism 340
III. GLP-1 in Satiety 342
IV. GLP-1 in GI Motility 343
V. GLP-1 in Perspective 346
Acknowledgments 346
References 347
Chapter 13: The Role of GLP-1 in Neuronal Activity and Neurodegeneration 350
I. A Causal Link Between Diabetes and Alzheimer's Disease 351
II. An Insulin-Supporting Messenger: Glucagon-Like Peptide-1 353
III. GLP-1 Analogues Have Neuroprotective Effects in Mouse Models of AD 361
IV. Many Other Growth Factors Show Neuroprotective Effects 365
Acknowledgments 366
References 366
Chapter 14: Wnt and Incretin Connections 374
I. What Are Incretins, What They Do, Where, and How 375
II. WNTs: What They Are and What They Do 379
III. WNT/beta-catenin Increases the Synthesis of Incretins 383
IV. Does WNT Influence Incretin Secretion? 388
V. Does WNT Influence Incretin Receptors and/or Their Signaling? 389
VI. Do Incretins Influence Wnt Signaling? GLP-1 Uses WNT Effectors in Pancreas 390
VII. What is the Meaning of the Wnt-Incretin Interplay for Health and Disease? 391
VIII. Perspectives 394
Acknowledgments 396
References 397
Chapter 15: Incretin-Based Therapy and Type 2 Diabetes 408
I. Introduction 409
II. The Incretin Hormones 411
III. Incretin Hormones in Type 2 Diabetes 415
IV. Incretin-Based Therapy 416
V. Conclusion and Perspectives 423
References 424
Chapter 16: GPR119 Agonists for the Potential Treatment of Type 2 Diabetes and Related Metabolic Disorders 434
I. Introduction 435
II. GPR119 Receptor Expression 437
III. GPR119 Signaling and Deorphanization 438
IV. GPR119 Agonism and Glucose Homeostasis 439
V. GPR119 Agonists: Medicinal Chemistry 442
VI. Conclusions 460
Acknowledgments 460
References 461
Index 468
Colour Plate 474