title: Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1.
abstract: The homeostasis of insulin-like growth factor-1 (IGF-1) is essential for metabolism, development and survival. Insufficient IGF-1 is associated with poor recovery from wounds whereas excessive IGF-1 contributes to growth of tumours. We have shown that cyclic glycine-proline (cGP), a metabolite of IGF-1, can normalise IGF-1 function by showing its efficacy in improving the recovery from ischemic brain injury in rats and inhibiting the growth of lymphomic tumours in mice. Further investigation in cell culture suggested that cGP promoted the activity of IGF-1 when it was insufficient, but inhibited the activity of IGF-1 when it was excessive. Mathematical modelling revealed that the efficacy of cGP was a modulated IGF-1 effect via changing the binding of IGF-1 to its binding proteins, which dynamically regulates the balance between bioavailable and non-bioavailable IGF-1. Our data reveal a novel mechanism of auto-regulation of IGF-1, which has physiological and pathophysiological consequences and potential pharmacological utility.
authors.affiliation: 1] Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand [2] Centre for Brain Research, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand [3] Gravida National Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.affiliation: 1] Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand [2] Gravida National Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Gluckman
authors.affiliation: 1] Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand [2] Centre for Brain Research, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Panzao
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Geoff
authors.initials: G
authors.lastname: Krissansen
authors.affiliation: Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun
authors.affiliation: 1] Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand [2] School of Pharmacy, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wen
authors.affiliation: 1] Institute of Natural and Mathematical Sciences, Massey University, Private Bag 102904, Auckland, New Zealand [2] AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton 3240, New Zealand.
authors.forename: Gemma
authors.initials: G
authors.lastname: Phillips
authors.affiliation: 1] Gravida National Centre for Growth and Development, University of Auckland, Auckland, New Zealand [2] AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton 3240, New Zealand [3] Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Shorten
authors.affiliation: 1] Gravida National Centre for Growth and Development, University of Auckland, Auckland, New Zealand [2] AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton 3240, New Zealand.
authors.forename: Chris D
authors.initials: CD
authors.lastname: McMahon
authors.affiliation: 1] Gravida National Centre for Growth and Development, University of Auckland, Auckland, New Zealand [2] Institute of Natural and Mathematical Sciences, Massey University, Private Bag 102904, Auckland, New Zealand [3] Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.
authors.forename: Graeme C
authors.initials: GC
authors.lastname: Wake
authors.affiliation: Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Wendy H K
authors.initials: WH
authors.lastname: Chan
authors.affiliation: AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton 3240, New Zealand.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Thomas
authors.affiliation: Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: April
authors.initials: A
authors.lastname: Ren
authors.affiliation: Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Steve
authors.initials: S
authors.lastname: Moon
authors.affiliation: Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, New Zealand.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D005998:Glycine / Q000737:chemistry; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D015233:Models, Statistical; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D010456:Peptides, Cyclic; D020011:Protective Agents; C519530:insulin-like growth factor-1, mouse; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D011392:Proline; D005998:Glycine