IGFs:Local Repair and Survival Factors Throughout Life Span (eBook)

Foreword 5
Acknowlegements 6
Contents 7
Contributors 9
GH & IGF1: Aspects of Global and Local Release and Actions
1 Introductory Remarks 12
2 IGF1: Global and Local Growth Factor 13
3 Access all Areas? 16
References 19
Hyperglycemia Regulates the Sensitivity of Vascular Cells to IGF- I Stimulation 22
1 Introduction 23
2 Role of Ligand Occupancy of aVb3 in Stimulating the Response to IGF- I 25
3 Augmentation of PI-3 Kinase Activation 26
4 Role of Hyperglycemia in Modulating aVb3/IGF-I Receptor- linked Signaling 27
5 In Vivo Validation that Cooperative Signaling Between aVb3 Integrin and the IGF- I Receptor Acceretes Atherosclerosis in Diabetes 28
References 29
IGFBP2 Supports ex vivo Expansion of Hematopoietic Stem Cells 32
1 Introduction 33
2 Materials and Methods 33
3 Culture Medium 34
4 Mouse HSC Culture 34
5 Human Cell Culture 34
6 Flow Cytometry 37
7 Competitive Reconstitution Analysis 38
8 NOD/SCID Transplant 41
9 Mass Spectrometry 41
10 Quantitative RT-PCR 44
11 Results 44
12 A Cocktail Including IGFBP2 Supports an Approximately 48- fold Increase in Numbers of Repopulating Mouse HSCs 46
13 IGFBP2 Stimulates Ex Vivo Expansion of Cultured Human Cord Blood CD133+ Cells 46
14 IGFBP2 and Angptl5 Together Stimulate Extensive Ex Vivo Expansion of SRCs of Cultured Human Cord Blood CD133+ Cells 47
15 IGFBP2 Upregulates HoxB Gene Expression 49
16 Discussion 49
References 50
The Role of Insulin-like Growth Factor-I in Central Nervous System Development 53
1 Introduction 53
2 Overview of IGF-I Effects on Brain Growth 54
3 Neural Stem and Progenitor Cells 56
4 Neurogenesis 58
5 Glia Development 60
6 Conclusions 63
References 64
Stimulation of Proliferative Pathways by IGF- binding Proteins 69
1 Introduction : The Insulin-like Growth Factors and Their Binding Proteins 70
2 Growth Inhibition by IGFBP-3 71
3 Growth Stimulation by IGFBP-3 71
4 Investigations into the Mechanism of Growth Stimulation by IGFBP- 3 72
5 Conclusion and Therapeutic Implications 75
References 76
Signaling Pathways that Regulate C. elegans Life Span 79
1 Gene Activities that Mediate Increased Life Span of C. Elegans Insulin- like Signaling Mutants 81
2 Life Span Regulation by Evolutionarily Conserved Genes Essential for Viability 84
3 Stress Response Systems Activated in Long-lived C. elegans 87
4 The Cherry-picked Longevity RNAi Library 88
5 Identification of C. elegans Genes Regulating Longevity using Enhanced RNAi- sensitive Strains 89
References 89
IGF-1 Regulation of Skeletal Muscle Hypertrophy and Atrophy 95
1 Protein Synthesis Pathways Downstream of IGF-1 96
2 Hypertrophy Mediators Downstream of PI3K and Akt: the Akt/ TORC1/ p70S6K and Akt/ GSK3 Pathways 96
3 A Second Hypertrophy Mediator downstream of PI3K and Akt: GSK3b 98
4 Skeletal Muscle Atrophy Occurs via Induction of Distinct E3 Ubiquitin Ligases, Whose Expression can be Inhibited by IGF- 1 99
5 IGF-1/PI3K/Akt Inhibition of FOXO Transcription Factors Blocks Upregulation of MuRF1 and MAFbx 100
6 IGF-1 Regulation of Myostatin 101
7 Conclusion 102
References 102
Growth Hormone, Insulin-like Growth Factor I and Insulin: their Relationship to Aging and Cancer 107
1 Introduction 107
2 GH/IGF-I/insulin axis in the aging process 108
3 Lessons from dwarf mice 109
4 Insulin receptor and insulin receptor substrates and life span 110
5 The role of GH/IGF/insulin axis in cancer promotion 110
6 Insulin receptor (IR) and insulin receptor substrates (IRS) and cancer 111
7 The importance of calorie restriction in aging and cancer 111
8 Summary and Conclusions 112
References 112
The Functions of Insulin-like Peptides in Insects 115
1 Introduction 116
2 The ILPs of Drosophila 118
3 ILPs in Other Insects 121
4 ILP-binding Proteins 126
5 Conclusions 130
References 130
IGF Receptors in the Adult Brain 135
1 Introduction 136
2 The Neuroprotective Action of IGF In Vitro and In Vivo 136
3 A Role for IGF Signaling in Neurodegenerative Disease 137
4 Experimental Ischemia/hypoxia as a Model for CVA 138
5 Exogenous Versus Endogenous IGF-I 140
6 Intracellular Mechanisms of Neuronal Death after H/I 141
7 IGF-I Action on Glial Cells 142
8 The Role of Edema in H/I Damage and Neuronal Death Following CNS Damage 144
9 Conclusion 145
References 146
The Role of the IGF-1 and its Partners in Central and Peripheral Metabolism: Considerations for Extending Healthy Life Span 153
1 IGF axis, age-related disease and longevity 154
2 IGF-1 and Glucose Metabolism 155
3 Central Regulation of Peripheral Glucose Metabolism 156
4 Regulation of Peripheral Glucose Metabolism by Hypothalamic IGF- 1 and its Receptor 156
5 IGFBP-3 and Glucose Metabolism: 157
6 Role of Central IGFBP-3 on Glucose Metabolism 158
7 Novel IGFBP-3 Binding Partner Humanin as a Regulator of Glucose Metabolism 159
8 Conclusions 160
References 161
Index 164