title: Mathematical modeling of the insulin signal transduction pathway for prediction of insulin sensitivity from expression data.
abstract: Mathematical models of biological pathways facilitate a systems biology approach to medicine. However, these models need to be updated to reflect the latest available knowledge of the underlying pathways. We developed a mathematical model of the insulin signal transduction pathway by expanding the last major previously reported model and incorporating pathway components elucidated since the original model was reported. Furthermore, we show that inputting gene expression data of key components of the insulin signal transduction pathway leads to sensible predictions of glucose clearance rates in agreement with reported clinical measurements. In one set of simulations, our model predicted that glycerol kinase knockout mice have reduced GLUT4 translocation, and consequently, reduced glucose uptake. Additionally, a comparison of our extended model with the original model showed that the added pathway components improve simulations of glucose clearance rates. We anticipate this expanded model to be a useful tool for predicting insulin sensitivity in mammalian tissues with altered expression protein phosphorylation or mRNA levels of insulin signal transduction pathway components.
authors.affiliation: Biomedical Engineering Interdepartmental Program, Henry Samueli School of Engineering and Applied Science at UCLA, USA.
authors.forename: Clark K
authors.initials: CK
authors.lastname: Ho
authors.affiliation: Biomedical Engineering Interdepartmental Program, Henry Samueli School of Engineering and Applied Science at UCLA, USA.
authors.forename: Lola
authors.initials: L
authors.lastname: Rahib
authors.affiliation: Biomedical Engineering Interdepartmental Program, Henry Samueli School of Engineering and Applied Science at UCLA, USA; Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Science at UCLA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
authors.affiliation: Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Science at UCLA, USA; Department of Human Genetics, David Geffen School of Medicine at UCLA, USA.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Sriram
authors.affiliation: Biomedical Engineering Interdepartmental Program, Henry Samueli School of Engineering and Applied Science at UCLA, USA; Department of Human Genetics, David Geffen School of Medicine at UCLA, USA; Department of Pediatrics, David Geffen School of Medicine at UCLA, USA; Mattel Children's Hospital at UCLA, USA. Electronic address: kdipple@ucla.edu.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Dipple
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D005991:Glycerol Kinase / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D005991:Glycerol Kinase; D005947:Glucose
keywords: Insulin sensitivity; Insulin signal transduction pathway; Mathematical modeling