Insulin and IGFs (eBook)

Front Cover 1
Vitamins and Hormones Insulin and IGFs 4
Copyright Page 5
Contents 8
Preface 16
Chapter 1: The Human Insulin Superfamily of Polypeptide Hormones 18
I. Introduction 19
II. Relaxin Peptide Hormone Subfamily 27
III. Concluding Remarks 39
Acknowledgments 39
References 39
Chapter 2: The Structure and Function of Insulin: Decoding the TR Transition 50
I. Introduction 51
II. Structure-Activity Relationships 55
III. Implications for the Genetics of Diabetes Mellitus 61
IV. Concluding Remarks 62
Acknowledgments 63
References 63
Chapter 3: Molecular Mechanisms of Differential Intracellular Signaling From the Insulin Receptor 68
I. Overview 69
II. Insulin and the IR 70
III. Modulation of IR Activity 74
IV. Differential Activation of the IR 80
V. Conclusions/Final Words 84
References 85
Chapter 4: c-Abl and Insulin Receptor Signalling 94
I. Introduction 95
II. Insulin and IGF-IRs 96
III. Metabolic Versus Mitogenic Effect of IR 100
IV. c-Abl Tyrosine Kinase 104
V. c-Abl and IR Signalling 110
VI. Concluding Remarks 115
Acknowledgments 116
References 116
Chapter 5: CXCL14 and Insulin Action 124
I. Introduction 125
II. Basic Properties of CXCL14 126
III. Biological Activities of CXCL14 130
IV. Novel Functions of CXCL14 Revealed by Knockout Mice 132
V. Signal Cross-Talk Between CXCL14 and Insulin 136
VI. CXCL14 as a Metabolic Regulator 136
VII. Conclusions 138
References 138
Chapter 6: Crosstalk Between Growth Hormone and Insulin Signaling 142
I. Introduction 143
II. GH Signaling 144
III. Insulin Signaling 147
IV. Regulation of GH Signaling by Insulin 148
V. Regulation of Insulin Signaling by Chronic GH 157
VI. Conclusions 159
Acknowledgments 160
References 160
Chapter 7: Intracellular Retention and Insulin-Stimulated Mobilization of GLUT4 Glucose Transporters 172
I. Introduction 173
II. GLUT4 Storage Vesicles (GSVs) 175
III. Insulin-Regulated Aminopeptidase (IRAP) 179
IV. Stability and Trafficking of GLUT4 and IRAP 181
V. TUG, an Essential Component of a Retention Receptor for GLUT4 183
VI. From What Membranes do GSVs Originate? 191
VII. A General Mechanism for the Regulated Targeting of Membrane Proteins 193
VIII. Conclusions 196
Acknowledgments 196
References 196
Chapter 8: Compartmentalization and Regulation of Insulin Signaling to GLUT4 by the Cytoskeleton 210
I. Introduction 211
II. Insulin Signaling to GLUT4 Vesicles 212
III. GLUT4 Vesicle Membrane Trafficking 217
IV. GLUT4 Vesicle Fusion 222
V. Conclusions 225
Acknowledgments 225
References 225
Chapter 9: Nutrient Modulation of Insulin Secretion 234
I. Introduction 235
II. Overview of Insulin Secretion 236
III. Nutrient Regulation of Insulin Secretion 241
References 255
Chapter 10: How Insulin Regulates Glucose Transport in Adipocytes 262
I. Introduction 263
II. Historical Perspective 267
III. Current Views and Controversies 282
IV. Conclusions and Future Directions 294
References 295
Chapter 11: Spatio-Temporal Dynamics of Phosphatidylinositol-3,4,5-Trisphosphate Signalling 304
I. Introduction 305
II. Synthesis and Degradation of PIP3 306
III. Real-Time Measurements of PIP3 in Living Cells 309
IV. Spatio-Temporal Patterns of PIP3 Signals 312
V. PIP3 Oscillations and Autocrine Insulin Signalling in beta-Cells 314
VI. Significance of PIP3 Oscillations 317
VII. Concluding Remarks 319
Acknowledgments 320
References 320
Chapter 12: Serine Kinases of Insulin Receptor Substrate Proteins 330
I. Introduction 331
II. Insulin and IGF-1 Signaling 331
III. Regulation of Insulin and IGF-1 Signaling: Role of Ser/Thr Phosphorylation of IRS Proteins 336
IV. The Consequences of Ser Phosphorylation of IRS Proteins 345
V. Ser Phosphorylation of IRS Proteins as an Array Phenomenon 350
VI. Summary 353
References 354
Chapter 13: Phosphorylation of IRS Proteins: Yin-Yang Regulation of Insulin Signaling 368
I. Introduction 369
II. Discovery of the IRS Proteins 370
III. Molecular Structure of the IRS Proteins 371
IV. Biological Function of IRS Proteins in Insulin Action 381
V. The Role of IRS Serine Phosphorylation in Mediating the Crosstalk with Other Signaling Pathways 383
VI. Mechanisms Underlying IRS Serine Phosphorylation-Induced Insulin Resistance 386
VII. Conclusion 389
References 390
Chapter 14: IRS-2 and Its Involvement in Diabetes and Aging 406
I. Introduction 407
II. Identification of IRS-2 Protein 408
III. Basic Structure of IRS Family Proteins 409
IV. Involvement of IRS Proteins in Other Signaling Pathways 409
V. IRS-2 Protein is Well Conserved Across Species 410
VI. IRS-2, and Its Regulation in Energy Homeostasis 410
VII. Searching for the Regulatory Factor of IRS-2 Transcription 412
VIII. Phenotype of IRS-2 Null Mice 414
IX. The Role of IRS-2 in Female Reproduction 417
X. The Putative Role of IRS-2 in Aging Process 417
XI. Summary 419
References 420
Chapter 15: Glucose-Dependent Insulinotropic Polypeptide (Gastric Inhibitory Polypeptide GIP)
I. Introduction 427
II. Glucose-Dependent Insulinotropic Polypeptide (GIP) 429
III. The GIP Gene and Precursor 432
IV. GIP Secretion and Metabolism 434
V. The GIP Receptor 438
VI. Actions of GIP 442
VII. GIP-Activated Signal-Transduction Pathways 449
VIII. Pathophysiology of GIP 456
Acknowledgments 461
References 461
Chapter 16: Insulin Granule Biogenesis, Trafficking and Exocytosis 490
I. Introduction 491
II. Section I 493
III. Section II 497
IV. Section III 501
V. Section IV 508
References 511
Chapter 17: Glucose, Regulator of Survival and Phenotype of Pancreatic Beta Cells 524
I. Scope 525
II. Beta Cell Handling of Glucose: Metabolic Specializations to Ensure Low-Affinity/High Capacity Glucose Sensing 526
III. Glucose as Regulator of the Differentiated Beta Cell Phenotype 529
IV. Glucose Regulation of Beta Cell Number 535
V. Beta Cell Handling of Threatening High and Low Glucose Levels 538
Acknowledgments 547
References 547
Chapter 18: Matrix Metalloproteinases, T Cell Homing and beta-Cell Mass in Type 1 Diabetes 558
I. Matrix Metalloproteinases and Their Natural Protein Inhibitors 559
II. T Cell Membrane Type-1 Matrix Metalloproteinase 564
III. Rodent Model of Human Type 1 Diabetes 567
IV. T Cell MT1-MMP and CD44 in T1D 569
Acknowledgment 573
References 573
Chapter 19: Role of Wnt Signaling in the Development of Type 2 Diabetes 580
I. Introduction 581
II. Wnt Signaling 582
III. TCF7L2 Variants and Type 2 Diabetes Risk 587
IV. Functional Relationship Between Wnt Signaling and Type 2 Diabetes In Vitro 591
V. Conclusions and Future Directions 592
References 595
Chapter 20: Retinal Insulin Receptor Signaling In Hyperosmotic Stress 600
I. Introduction 601
II. Experimental Procedures 603
III. Results 607
IV. Discussion 620
Acknowledgments 624
References 625
Chapter 21: Interleukin-6 and Insulin Resistance 630
I. Introduction 631
II. Insulin Signaling and Insulin Resistance 632
III. IL-6 and Insulin Resistance 636
IV. Conclusions 642
Acknowledgment 643
References 644
Chapter 22: Structure, Function, and Regulation of Insulin-Degrading Enzyme 652
I. Introduction 653
II. Structure of IDE 654
III. The Regulation of IDE Activity 659
IV. Conclusion 662
Acknowledgments 662
References 662
Chapter 23: Modification of Androgen Receptor Function by Igf-1 Signaling: Implications in the Mechanism of Refractory Prostate Carcinoma 666
I. Androgen Receptor Signaling 668
II. IGF Signaling and Foxo-1 670
III. Interaction between AR and Insulin/IGF-1 Signaling 671
IV. Clinical Implications of Interactions between IGF-1 Signaling and AR 676
V. Conclusion 679
Acknowledgments 680
References 680
Chapter 24: Insulin-Like Growth Factor-2/Mannose-6 Phosphate Receptors 684
I. Introduction 685
II. The IGF-2/M6P Receptor 688
III. Functions of the IGF-2/M6P Receptor 695
IV. Conclusions 702
References 702
Chapter 25: Interactions of IGF-II with the IGF2R/Cation-Independent Mannose-6-Phosphate Receptor: Mechanism and Biological Outcomes 716
I. Introduction 717
II. The Mechanism of the IGF2R:IGF-II Interaction 718
III. Conclusion 730
References 731
Index 738
Color Plates 751