The authors declared that they have no conflicts of interest.
A novel method for simulating insulin mediated GLUT4 translocation
Article first published online: 5 AUG 2014
© 2014 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 111, Issue 12, pages 2454–2465, December 2014
How to Cite
Jezewski, A. J., Larson, J. J., Wysocki, B., Davis, P. H. and Wysocki, T. (2014), A novel method for simulating insulin mediated GLUT4 translocation. Biotechnol. Bioeng., 111: 2454–2465. doi: 10.1002/bit.25310
Andrew J. Jezewski and Joshua J. Larson contributed equally to this work.
- Issue published online: 27 OCT 2014
- Article first published online: 5 AUG 2014
- Accepted manuscript online: 11 JUN 2014 03:43AM EST
- Manuscript Accepted: 5 JUN 2014
- Manuscript Revised: 22 APR 2014
- Manuscript Received: 27 AUG 2013
- National Center for Research Resources. Grant Number: 5P20RR016469
- National Institute for General Medical Science (NIGMS). Grant Number: 8P20GM103427
- computational modeling;
- queuing theory
Glucose transport in humans is a vital process which is tightly regulated by the endocrine system. Specifically, the insulin hormone triggers a cascade of intracellular signals in target cells mediating the uptake of glucose. Insulin signaling triggers cellular relocalization of the glucose transporter protein GLUT4 to the cell surface, which is primarily responsible for regulated glucose import. Pathology associated with the disruption of this pathway can lead to metabolic disorders, such as type II diabetes mellitus, characterized by the failure of cells to appropriately uptake glucose from the blood. We describe a novel simulation tool of the insulin intracellular response, incorporating the latest findings regarding As160 and GEF interactions. The simulation tool differs from previous computational approaches which employ algebraic or differential equations; instead, the tool incorporates statistical variations of kinetic constants and initial molecular concentrations which more accurately mimic the intracellular environment. Using this approach, we successfully recapitulate observed in vitro insulin responses, plus the effects of Wortmannin-like inhibition of the pathway. The developed tool provides insight into transient changes in molecule concentrations throughout the insulin signaling pathway, and may be employed to identify or evaluate potentially critical components of this pathway, including those associated with insulin resistance. In the future, this highly tractable platform may be useful for simulating other complex cell signaling pathways. Biotechnol. Bioeng. 2014;111: 2454–2465. © 2014 Wiley Periodicals, Inc.