A novel method for simulating insulin mediated GLUT4 translocation

Andrew J. Jezewski, Joshua J. Larson, Beata Wysocki, Paul H Davis, Tadeusz A Wysocki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2454-2465
Number of pages12
JournalBiotechnology and Bioengineering
Volume111
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Insulin
Glucose
Glucose Transporter Type 4
Endocrine System
Critical Pathways
Facilitative Glucose Transport Proteins
Cell signaling
Type 2 Diabetes Mellitus
Hormones
Pathology
Insulin Resistance
Blood Glucose
Medical problems
Blood
Differential equations
Proteins
Molecules
Kinetics

Keywords

  • Computational modeling
  • GLUT4
  • Insulin
  • Metabolism
  • Queuing theory

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

A novel method for simulating insulin mediated GLUT4 translocation. / Jezewski, Andrew J.; Larson, Joshua J.; Wysocki, Beata; Davis, Paul H; Wysocki, Tadeusz A.

In: Biotechnology and Bioengineering, Vol. 111, No. 12, 01.12.2014, p. 2454-2465.

Research output: Contribution to journalArticle

Jezewski, Andrew J. ; Larson, Joshua J. ; Wysocki, Beata ; Davis, Paul H ; Wysocki, Tadeusz A. / A novel method for simulating insulin mediated GLUT4 translocation. In: Biotechnology and Bioengineering. 2014 ; Vol. 111, No. 12. pp. 2454-2465.
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