Insulin resistance is a primary defect underlying the development of type II diabetes. In healthy conditions, insulin stimulates glucose uptake from the blood stream, but in diseased conditions the normal metabolic response is impaired. Identifying specific drug targets to restore insulin sensitivity at the cellular level and developing an effective treatment strategy require insight into both the biochemical mechanisms involved and the whole signalling network response to external cues. This study focuses on the consequences of integrating a detailed biochemical description of the insulin receptor trafficking compartment within a phenomenological model of the downstream signalling pathway. While the description of the experimental data is preserved by an iterative procedure of parameter fitting, the dynamic response of the network is highly modified, as shown by analyzing the complementary information derived from studying both connection sensitivities and node noise in the network. This is crucial considering the importance of network dynamics for identifying effective drug targets.
|Original language||English (US)|
|Title of host publication||DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts|
|Number of pages||6|
|State||Published - 2010|
|Event||9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010 - Leuven, Belgium|
Duration: Jul 5 2010 → Jul 7 2010
|Name||IFAC Proceedings Volumes (IFAC-PapersOnline)|
|Other||9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010|
|Period||7/5/10 → 7/7/10|
Bibliographical noteFunding Information:
⋆This work was funded by Pfizer Inc. K.S. and L.P. were also supported by Grant No. R01EB007511 from the National Institute of Biomedical Imaging and Bioengineering, DOE Contract No. DE-FG02-04ER25621, NSF Contract No. IGERT DG02-21715, and the Institute for Collaborative Biotechnologies through Grant No. DFR3A-8-447850-23002 from the U.S. Army Research Office. K.S. was supported by a National Science Foundation Graduate Research Fellowship.
- Drug target
- Sensitivity analysis
- Signalling pathway
- Stochastic modelling