1;Foreword;5 2;Acknowlegements;6 3;Contents;7 4;Contributors;9 5;GH & IGF1: Aspects of Global and Local Release and Actions;12 5.1;1 Introductory Remarks;12 5.2;2 IGF1: Global and Local Growth Factor;13 5.3;3 Access all Areas?;16 5.4;References;19 6;Hyperglycemia Regulates the Sensitivity of Vascular Cells to IGF- I Stimulation;22 6.1;1 Introduction;23 6.2;2 Role of Ligand Occupancy of aVb3 in Stimulating the Response to IGF- I;25 6.3;3 Augmentation of PI-3 Kinase Activation;26 6.4;4 Role of Hyperglycemia in Modulating aVb3/IGF-I Receptor- linked Signaling;27 6.5;5 In Vivo Validation that Cooperative Signaling Between aVb3 Integrin and the IGF- I Receptor Acceretes Atherosclerosis in Diabetes;28 6.6;References;29 7;IGFBP2 Supports ex vivo Expansion of Hematopoietic Stem Cells;32 7.1;1 Introduction;33 7.2;2 Materials and Methods;33 7.3;3 Culture Medium;34 7.4;4 Mouse HSC Culture;34 7.5;5 Human Cell Culture;34 7.6;6 Flow Cytometry;37 7.7;7 Competitive Reconstitution Analysis;38 7.8;8 NOD/SCID Transplant;41 7.9;9 Mass Spectrometry;41 7.10;10 Quantitative RT-PCR;44 7.11;11 Results ;44 7.12;12 A Cocktail Including IGFBP2 Supports an Approximately 48- fold Increase in Numbers of Repopulating Mouse HSCs;46 7.13;13 IGFBP2 Stimulates Ex Vivo Expansion of Cultured Human Cord Blood CD133+ Cells;46 7.14;14 IGFBP2 and Angptl5 Together Stimulate Extensive Ex Vivo Expansion of SRCs of Cultured Human Cord Blood CD133+ Cells;47 7.15;15 IGFBP2 Upregulates HoxB Gene Expression;49 7.16;16 Discussion;49 7.17;References;50 8;The Role of Insulin-like Growth Factor-I in Central Nervous System Development;53 8.1;1 Introduction;53 8.2;2 Overview of IGF-I Effects on Brain Growth;54 8.3;3 Neural Stem and Progenitor Cells;56 8.4;4 Neurogenesis;58 8.5;5 Glia Development;60 8.6;6 Conclusions;63 8.7;References;64 9;Stimulation of Proliferative Pathways by IGF- binding Proteins;69 9.1;1 Introduction : The Insulin-like Growth Factors and Their Binding Proteins;70 9.2;2 Growth Inhibition by IGFBP-3;71 9.3;3 Growth Stimulation by IGFBP-3;71 9.4;4 Investigations into the Mechanism of Growth Stimulation by IGFBP- 3;72 9.5;5 Conclusion and Therapeutic Implications;75 9.6;References;76 10;Signaling Pathways that Regulate C. elegans Life Span;79 10.1;1 Gene Activities that Mediate Increased Life Span of C. Elegans Insulin- like Signaling Mutants;81 10.2;2 Life Span Regulation by Evolutionarily Conserved Genes Essential for Viability;84 10.3;3 Stress Response Systems Activated in Long-lived C. elegans;87 10.4;4 The Cherry-picked Longevity RNAi Library;88 10.5;5 Identification of C. elegans Genes Regulating Longevity using Enhanced RNAi- sensitive Strains;89 10.6;References;89 11;IGF-1 Regulation of Skeletal Muscle Hypertrophy and Atrophy;95 11.1;1 Protein Synthesis Pathways Downstream of IGF-1;96 11.2;2 Hypertrophy Mediators Downstream of PI3K and Akt: the Akt/ TORC1/ p70S6K and Akt/ GSK3 Pathways;96 11.3;3 A Second Hypertrophy Mediator downstream of PI3K and Akt: GSK3b;98 11.4;4 Skeletal Muscle Atrophy Occurs via Induction of Distinct E3 Ubiquitin Ligases, Whose Expression can be Inhibited by IGF- 1;99 11.5;5 IGF-1/PI3K/Akt Inhibition of FOXO Transcription Factors Blocks Upregulation of MuRF1 and MAFbx;100 11.6;6 IGF-1 Regulation of Myostatin;101 11.7;7 Conclusion;102 11.8;References;102 12;Growth Hormone, Insulin-like Growth Factor I and Insulin: their Relationship to Aging and Cancer;107 12.1;1 Introduction;107 12.2;2 GH/IGF-I/insulin axis in the aging process;108 12.3;3 Lessons from dwarf mice;109 12.4;4 Insulin receptor and insulin receptor substrates and life span;110 12.5;5 The role of GH/IGF/insulin axis in cancer promotion;110 12.6;6 Insulin receptor (IR) and insulin receptor substrates (IRS) and cancer;111 12.7;7 The importance of calorie restriction in aging and cancer;111 12.8;8 Summary and Conclusions;112 12.9;References;112 13;The Functions of Insulin-like Peptides in Insects;115 13.1;1 Introduction;116 13.2;2 The ILPs of Drosophila;118 13.3;3 ILPs in Ot