title: Modeling the effect of insulin-like growth factor-1 on human cell growth.
abstract: Insulin-like growth factor-1 (IGF-1) plays a key role in human growth and development. The interactions of IGF-1 with IGF-1 receptors and IGF-1 binding proteins (IGFBPs) regulate IGF-1 function. Recent research suggests that a metabolite of IGF-1, cyclo-glycyl-proline (cGP), has a role in regulating IGF-1 homeostasis. A component of this interaction is believed to be the competitive binding of IGF-1 and cGP to IGFBPs. In this paper we describe a mathematical model of the interaction between IGF-1 and cGP on human cell growth. The model can be used to understand the interaction between IGF-1, IGFBPs, cGP and IGF-1 receptors along with the kinetics of cell growth. An explicit model of the known interactions between IGF-1, cGP, IGFBPs, IGF-1 receptors explained a large portion of the variance in cell growth (R(2) = 0.83). An implicit model of the interactions between IGF-1, cGP, IGFBPs, IGF-1 receptors that included a hypothesized feedback of cGP on IGF-1 receptors explained nonlinear features of interaction between IGF-1 and cGP not described by the explicit model (R(2) = 0.84). The model also explained the effect of IGFBP antibody on the interaction between cGP and IGF-1 (R(2) = 0.78). This demonstrates that the competitive binding of IGF-1 and cGP to IGFBPs plays a large role in the interaction between IGF-1 and cGP, but that other factors potentially play a role in the interaction between cGP and IGF-1. These models can be used to predict the complex interaction between IGF-1 and cGP on human cell growth and form a basis for further research in this field.
authors.affiliation: Institute of Natural and Mathematical Sciences, Massey University at Albany, Private Bag 102904, North Shore MC, Auckland, New Zealand. Electronic address: gphi024@aucklanduni.ac.nz.
authors.forename: Gemma M A
authors.initials: GM
authors.lastname: Phillips
authors.affiliation: AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand; Gravida National Centre for Growth and Development, University of Auckland, Private Bag 92019, Auckland, New Zealand. Electronic address: paul.shorten@agresearch.co.nz.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Shorten
authors.affiliation: Institute of Natural and Mathematical Sciences, Massey University at Albany, Private Bag 102904, North Shore MC, Auckland, New Zealand; Gravida National Centre for Growth and Development, University of Auckland, Private Bag 92019, Auckland, New Zealand. Electronic address: g.c.wake@massey.ac.nz.
authors.forename: Graeme C
authors.initials: GC
authors.lastname: Wake
authors.affiliation: Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand; Gravida National Centre for Growth and Development, University of Auckland, Private Bag 92019, Auckland, New Zealand; Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand. Electronic address: j.guan@auckland.ac.nz.
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
mesh_terms: D048708:Cell Growth Processes; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I
keywords: Dynamic modeling; Insulin-like growth factor 1; Model testing,; Simulation; Steady state analysis