Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway

Camilla Luni; Kevin R. Sanft; Linda R. Petzold; Francis J. Doyle

doi:10.3182/20100705-3-BE-2011.0059

Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway

Camilla Luni, Kevin R. Sanft, Linda R. Petzold, Francis J. Doyle

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

1 Scopus citations

Abstract

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
Pages	326-331
Number of pages	6
Edition	PART 1
DOIs	https://doi.org/10.3182/20100705-3-BE-2011.0059
State	Published - 2010
Externally published	Yes
Event	9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010 - Leuven, Belgium Duration: Jul 5 2010 → Jul 7 2010

Publication series

Name	IFAC Proceedings Volumes (IFAC-PapersOnline)
Number	PART 1
Volume	9
ISSN (Print)	1474-6670

Other

Other	9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010
Country/Territory	Belgium
City	Leuven
Period	7/5/10 → 7/7/10

Bibliographical note

Funding 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.

Keywords

Diabetes
Drug target
Insulin
Sensitivity analysis
Signalling pathway
Stochastic modelling

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.3182/20100705-3-BE-2011.0059

Find It

Find It at U of M Libraries

Cite this

Luni, C., Sanft, K. R., Petzold, L. R., & Doyle, F. J. (2010). Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway. In DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts (PART 1 ed., pp. 326-331). (IFAC Proceedings Volumes (IFAC-PapersOnline); Vol. 9, No. PART 1). https://doi.org/10.3182/20100705-3-BE-2011.0059

Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway. / Luni, Camilla; Sanft, Kevin R.; Petzold, Linda R. et al.
DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts. PART 1. ed. 2010. p. 326-331 (IFAC Proceedings Volumes (IFAC-PapersOnline); Vol. 9, No. PART 1).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Luni, C, Sanft, KR, Petzold, LR & Doyle, FJ 2010, Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway. in DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts. PART 1 edn, IFAC Proceedings Volumes (IFAC-PapersOnline), no. PART 1, vol. 9, pp. 326-331, 9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010, Leuven, Belgium, 7/5/10. https://doi.org/10.3182/20100705-3-BE-2011.0059

Luni C, Sanft KR, Petzold LR, Doyle FJ. Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway. In DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts. PART 1 ed. 2010. p. 326-331. (IFAC Proceedings Volumes (IFAC-PapersOnline); PART 1). doi: 10.3182/20100705-3-BE-2011.0059

@inproceedings{19d6dcb8644a4abc840281f5bd5ba193,

title = "Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway",

abstract = "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.",

keywords = "Diabetes, Drug target, Insulin, Sensitivity analysis, Signalling pathway, Stochastic modelling",

author = "Camilla Luni and Sanft, {Kevin R.} and Petzold, {Linda R.} and Doyle, {Francis J.}",

note = "Funding 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.; 9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010 ; Conference date: 05-07-2010 Through 07-07-2010",

year = "2010",

doi = "10.3182/20100705-3-BE-2011.0059",

language = "English (US)",

isbn = "9783902661692",

series = "IFAC Proceedings Volumes (IFAC-PapersOnline)",

number = "PART 1",

pages = "326--331",

booktitle = "DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts",

edition = "PART 1",

}

TY - GEN

T1 - Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway

AU - Luni, Camilla

AU - Sanft, Kevin R.

AU - Petzold, Linda R.

AU - Doyle, Francis J.

N1 - Funding 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.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Diabetes

KW - Drug target

KW - Insulin

KW - Sensitivity analysis

KW - Signalling pathway

KW - Stochastic modelling

UR - http://www.scopus.com/inward/record.url?scp=80051740617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051740617&partnerID=8YFLogxK

U2 - 10.3182/20100705-3-BE-2011.0059

DO - 10.3182/20100705-3-BE-2011.0059

M3 - Conference contribution

AN - SCOPUS:80051740617

SN - 9783902661692

T3 - IFAC Proceedings Volumes (IFAC-PapersOnline)

SP - 326

EP - 331

BT - DYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts

T2 - 9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010

Y2 - 5 July 2010 through 7 July 2010

ER -

Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway

Abstract

Publication series

Other

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this