Insulin and IGFs Book

Contributors xv

Preface xxi

1 The Human Insulin Superfamily of Polypeptide Hormones Fazel Shabanpoor Frances Separovic John D. Wade 1

I Introduction 2

II Relaxin Peptide Hormone Subfamily 10

III Concluding Remarks 22

Acknowledgments 22

References 22

2 The Structure and Function of Insulin: Decoding the TR Transition Michael A. Weiss 33

I Introduction 34

II Structure-Activity Relationships 38

III Implications for the Genetics of Diabetes Mellitus 44

IV Concluding Remarks 45

Acknowledgments 46

References 46

3 Molecular Mechanisms of Differential Intracellular Signaling From the Insulin Receptor Maja Jensen Pierre De Meyts 51

I Overview 52

II Insulin and the IR 53

III Modulation of IR Activity 57

IV Differential Activation of the IR 63

V Conclusions/Final Words 67

References 68

4 c-Abl and Insulin Receptor Signalling Marco Genua Giuseppe Pandini Maria Francesca Cassarino Rosa Linda Messina Francesco Frasca 77

I Introduction 78

II Insulin and IGF-IRs 79

III Metabolic Versus Mitogenic Effect of IR 83

IV c-Abl Tyrosine Kinase 87

V c-Abl and IR Signalling 93

VI Concluding Remarks 98

Acknowledgments 99

References 99

5 CXCL14 and Insulin Action Takahiko Hara Yuki Nakayama 107

I Introduction 108

II Basic Properties ofCXCL14 109

III Biological Activities of CXCL14 113

IV Novel Functions ofCXCL14 Revealed by Knockout Mice 115

V Signal Cross-Talk Between CXCL14and Insulin 119

VI CXCL14as a Metabolic Regulator 119

VII Conclusions 121

References 121

6 Crosstalk Between Growth Hormone and Insulin Signaling Jie Xu Joseph L. Messina 125

I Introduction 126

II GH Signaling 127

III Insulin Signaling 130

IV Regulationof GH Signaling by Insulin 131

V Regulation of Insulin Signaling by Chronic GH 140

VI Conclusions 142

Acknowledgments 143

References 143

7 Intracellular Retention and Insulin-Stimulated Mobilization of <$$$> Glucose Transporters Bradley R. Rubin Jonathan S. Bogan 155

I Introduction 156

II <$$$> Storage Vesicles (GSVs) 158

III Insulin-Regulated Aminopeptidase (IRAP) 162

IV Stability and Trafficking of <$$$> and IRAP 164

V TUG, an Essential Component of a Retention Receptor for <$$$> 166

VI From What Membranes do GSVs Originate? 174

VII A General Mechanism for the Regulated Targeting of Membrane Proteins 176

VIII Conclusions 179

Acknowledgments 179

References 179

8 Compartmentalization and Regulation of Insulin Signaling to <$$$> by the Cytoskeleton Craig A. Eyster Ann Louise Olson 193

I Introduction 194

II Insulin Signaling to <$$$> Vesicles 195

III <$$$> Vesicle Membrane Trafficking 200

IV <$$$> Vesicle Fusion 205

V Conclusions 208

Acknowledgments 208

References 208

9 Nutrient Modulation of Insulin Secretion Nimbe Torres Lilia Noriega Armando R. Tovar 217

I Introduction 218

II Overview of Insulin Secretion 219

III Nutrient Regulation of Insulin Secretion 224

References 238

10 How Insulin Regulates Glucose Transport in Adipocytes Joseph M. Muretta Cynthia Corley Mastick 245

I Introduction 246

II Historical Perspective 250

III Current Views and Controversies 265

IV Conclusions and Future Directions 277

References 278

11 Spatio-Temporal Dynamics of Phosphatidylinositol-3,4,5-Trisphosphate Signalling Anders Tengholm Olof Idevall-Hagren 287

I Introduction 288

II Synthesis and Degradation of <$$$> 289

III Real-Time Measurements of <$$$> in Living Cells 292

IV Spatio-Temporal Patterns of <$$$> Signals 295

V <$$$> Oscillations and Autocrine Insulin Signalling in β-Cells 297

VI Significance of <$$$> Oscillations 300

VII Concluding Remarks 302

Acknowledgments 303

References 303

12 Serine Kinases of Insulin Receptor Substrate Proteins Sigalit Boura-Halfon Yehiel Zick 313

I Introduction 314

II Insulin and IGF-1 Signaling 314

III Regulation of Insulin and IGF-1 Signaling: Role of Ser/Thr Phosphorylation of IRS Proteins 319

IV The Consequences of Ser Phosphorylation of IRS Proteins 328

V Ser Phosphorylation of IRS Proteins as an Array Phenomenon 333

VI Summary 336

References 337

13 Phosphorylation of IRS Proteins: Yin-Yang Regulation of Insulin Signaling Xiao Jian Sun Feng Liu 351

I Introduction 352

II Discovery of the IRS Proteins 353

III Molecular Structure of the IRS Proteins 354

IV Biological Function of IRS Proteins in Insulin Action 364

V The Role of IRS Serine Phosphorylation in Mediating the Crosstalk with Other Signaling Pathways 366

VI Mechanisms Underlying IRS Serine Phosphorylation-Induced Insulin Resistance 369

VII Conclusion 372

References 373

14 IRS-2 and Its Involvement in Diabetes and Aging Jiandi Zhang Tian-Qiang Sun 389

I Introduction 390

II Identification of IRS-2 Protein 391

III Basic Structure of IRS Family Proteins 392

IV Involvement of IRS Proteins in Other Signaling Pathways 392

V IRS-2 Protein is Well Conserved Across Species 393

VI IRS-2, and Its Regulation in Energy Homeostasis 393

VII Searching for the Regulatory Factor of IRS-2 Transcription 395

VIII Phenotype of IRS-2 Null Mice 397

IX The Role of IRS-2 in Female Reproduction 400

X The Putative Role of IRS-2 in Aging Process 400

XI Summary 402

References 403

15 Glucose-Dependent Insulinotropic Polypeptide (Gastric Inhibitory Polypeptide; GIP) Christopher H. S. McIntosh Scott Widenmaier Su-Jin Kim 409

I Introduction 410

II Glucose-Dependent Insulinotropic Polypeptide (GIP) 412

III The GIP Gene and Precursor 415

IV GIP Secretion and Metabolism 417

V The GIP Receptor 421

VI Actions of GIP 425

VII GIP-Activated Signal-Transduction Pathways 432

VIII Pathophysiology of GIP 439

Acknowledgments 444

References 444

16 Insulin Granule Biogenesis, Trafficking and Exocytosis June Chunqiu Hou Le Min Jeffrey E. Pessin 473

I Introduction 474

II Section I 476

III Section II 480

IV Section III 484

V Section IV 491

References 494

17 Glucose, Regulator of Survival and Phenotype of Pancreatic Beta Cells Geert A. Martens Daniel Pipeleers 507

I Scope 508

II Beta Cell Handling of Glucose: Metabolic Specializations to Ensure Low-Affinity/High Capacity Glucose Sensing 509

III Glucose as Regulator of the Differentiated Beta Cell Phenotype 512

IV Glucose Regulation of Beta Cell Number 518

V Beta Cell Handing of Threatening High and Low Glucose Levels 521

Acknowledgments 530

References 530

18 Matrix Metalloproteinases, T Cell Homing and β-Cell Mass in Type 1 Diabetes Alexei Y. Savinov Alex Y. Strongin 541

I Matrix Metalloproteinases and Their Natural Protein Inhibitors 542

II T Cell Membrane Type-1 Matrix Metalloproteinase 547

III Rodent Model of Human Type 1 Diabetes 550

IV T Cell MT1-MMP and CD44 in T1D 552

Acknowledgment 556

References 556

19 Role of Wnt Signaling in the Development of Type 2 Diabetes Michael Bordonaro 563

I Introduction 564

II Wnt Signaling 565

III TCF7L2 Variants and Type 2 Diabetes Risk 570

IV Functional Relationship Between Wnt Signaling and Type 2 Diabetes In Vitro 574

V Conclusions and Future Directions 575

References 578

20 Retinal Insulin Receptor Signaling In Hyperosmotic Stress Raju V. S. Rajala Ivana Ivanovic Ashok Kumar Dilly 583

I Introduction 584

II Experimental Procedures 586

III Results 590

IV Discussion 603

Acknowledgments 607

References 608

21 Interleukin-6 and Insulin Resistance Jeong-Ho Kim Rebecca A. Bachmann Jie Chen 613

I Introduction 614

II Insulin Signaling and Insulin Resistance 615

III IL-6 and Insulin Resistance 619

IV Conclusions 625

Acknowledgment 626

References 627

22 Structure, Function, and Regulation of Insulin-Degrading Enzyme Raymond E. Hulse Luis A. Ralat Wei-Jen Tang 635

I Introduction 636

II Structure of IDE 637

III The Regulation of IDE Activity 642

IV Conclusion 645

Acknowledgments 645

References 645

23 Modification of Androgen Receptor Function by Igf-1 Signaling: Implications in the Mechanism of Refractory Prostate Carcinoma Toshihiko Yanase WuQiang Fan 649

I Androgen Receptor Signaling 651

II IGF Signaling and Foxo-1 653

III Interaction between AR and Insulin/IGF-1 Signaling 654

IV Clinical Implications of Interactions between IGF-1 Signaling and AR 659

V Conclusion 662

Acknowledgments 663

References 663

24 Insulin-Like Growth Factor-2/Mannose-6 Phosphate Receptors Hesham M. El-Shewy Louis M. Luttrell 667

I Introduction 668

II The IGF-2/M6P Receptor 671

III Functions of the IGF-2/M6P Receptor 678

IV Conclusions 685

References 685

25 Interactions of IGF-II with the IGF2R/Cation-Independent Mannose-6-Phosphate Receptor: Mechanism and Biological Outcomes J. Brown, E. Y. Jones B. E. Forbes 699

I Introduction 700

II The Mechanism of the IGF2R:IGF-II Interaction 701

III Conclusion 713

References 714

Index 721