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March  2013, 8(1): 65-78. doi: 10.3934/nhm.2013.8.65

Growth regulation and the insulin signaling pathway

Peter W. Bates 1, , Yu Liang 1, and  Alexander W. Shingleton 2,

1. 

Department of Mathematics, Michigan State University, East Lansing, MI 48824, United States, United States
2. 

Department of Zoology, Michigan State University, East Lansing, MI 48824, United States

Received  April 2012 Revised  January 2013 Published  April 2013

The insulin signaling pathway propagates a signal from receptors in the cell membrane to the nucleus via numerous molecules some of which are transported through the cell in a partially stochastic way. These different molecular species interact and eventually regulate the activity of the transcription factor FOXO, which is partly responsible for inhibiting the growth of organs. It is postulated that FOXO partially governs the plasticity of organ growth with respect to insulin signalling, thereby preserving the full function of essential organs at the expense of growth of less crucial ones during starvation conditions. We present a mathematical model of this reacting and directionally-diffusing network of molecules and examine the predictions resulting from simulations.
Keywords: signaling pathway, nonlinear system of partial differential equations., Cellular regulatory network.
Mathematics Subject Classification: Primary: 92-08, 92C42, 92C40; Secondary: 92C37, 92C3.
Citation: Peter W. Bates, Yu Liang, Alexander W. Shingleton. Growth regulation and the insulin signaling pathway. Networks and Heterogeneous Media, 2013, 8 (1) : 65-78. doi: 10.3934/nhm.2013.8.65
References:
[1]

Robert P. Erickson, Zhiyuan Jia, Steven P. Gross and Clare C. Yu, How molecular motors are arranged on a cargo is important for vesicular transport, PLoS Comput Biol., 7 (2011), 1-22.

[2]

Ahmed Essaghir, Nicolas Dif, Catherine Y. Marbehant, Paul J. Coffer and Jean-Baptiste Demoulin, The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors, J. Biol. Chem., 284 (2009), 10334-10342. doi: 10.1074/jbc.M808848200.

[3]

Geert J. Kops, Nancy D. de Ruiter, Alida M. Vries-Smits, David R. Powell, Johannes L. Bos and Boudewijn M. Burgering, Direct control of the Forkhead transcription factor AFX by protein kinase B, Nature, 398 (1999), 630-634.

[4]

Hitomi Matsuzaki, Hiroaki Daitoku, Mitsutoki Hatta, Keiji Tanaka and Akiyoshi Fukamizu, Insulin- induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation, Proc. Natl. Acad. Sci. U S A, 100 (2003), 11285-11290. doi: 10.1073/pnas.1934283100.

[5]

Oscar Puig and Robert Tjian, Transcriptional feedback control of insulin receptor by dFOXO/FOXO1, Genes & Dev., 19 (2005), 2435-2446. doi: 10.1101/gad.1340505.

[6]

Michael J. Quon and L. A. Campfield, A mathematical model and computer simulation study of insulin receptor regulation, J. Theor. Biol., 150 (1991), 59-72. doi: 10.1016/S0022-5193(05)80475-8.

[7]

Michael J. Quon and L. A. Campfield, A mathematical model and computer simulation study of insulin-sensitive glucose transporter regulation, J. Theor. Biol., 150 (1991), 93-107. doi: 10.1016/S0022-5193(05)80477-1.

[8]

Jaime Resino and Antonio García-Bellido, Drosophila genetic variants that change cell size and rate of proliferation affect cell communication and hence patterning, Mechanisms of Development, 121 (2004), 351-364. doi: 10.1016/j.mod.2004.02.007.

[9]

Ahmad R. Sedaghat, Arthur Sherman and Michael J. Quon, A mathematical model of metabolic insulin signaling pathways, Am. J. Physiol. Endocrinol. Metab., 283 (2002), 84-101.

[10]

Alexander W. Shingleton, The regulation of organ size in drosophila, Organogenesis, 6 (2010), 1-13.

[11]

Graham R. Smith and Daryl P. Shanley, Modelling the response of FOXO transcription factor to multiple post-translational modifications made by ageing-related signalling pathways, PLoS ONE, 5 (2010), 1-18. doi: 10.1371/journal.pone.0011092.

[12]

Huiyuan Tang, Martha S. B. Smith-Caldas, Michael V. Driscoll, Samy Salhadar and Alexander W. Shingleton, FOXO regulates organ-specific phenotypic plasticity in drosophila, PLoS Genet., 7 (2011), 1-12. doi: 10.1371/journal.pgen.1002373.

[13]

Lars P. Van Der Heide, Marco F. M. Hoekman and Marten P. Smidt, The ins and outs of FoxO shuttling: Mechanism of FoxO translocation and transcriptional regulation, Biochem. J., 380 (2004), 297-309.

show all references

References:
[1]

Robert P. Erickson, Zhiyuan Jia, Steven P. Gross and Clare C. Yu, How molecular motors are arranged on a cargo is important for vesicular transport, PLoS Comput Biol., 7 (2011), 1-22.

[2]

Ahmed Essaghir, Nicolas Dif, Catherine Y. Marbehant, Paul J. Coffer and Jean-Baptiste Demoulin, The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors, J. Biol. Chem., 284 (2009), 10334-10342. doi: 10.1074/jbc.M808848200.

[3]

Geert J. Kops, Nancy D. de Ruiter, Alida M. Vries-Smits, David R. Powell, Johannes L. Bos and Boudewijn M. Burgering, Direct control of the Forkhead transcription factor AFX by protein kinase B, Nature, 398 (1999), 630-634.

[4]

Hitomi Matsuzaki, Hiroaki Daitoku, Mitsutoki Hatta, Keiji Tanaka and Akiyoshi Fukamizu, Insulin- induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation, Proc. Natl. Acad. Sci. U S A, 100 (2003), 11285-11290. doi: 10.1073/pnas.1934283100.

[5]

Oscar Puig and Robert Tjian, Transcriptional feedback control of insulin receptor by dFOXO/FOXO1, Genes & Dev., 19 (2005), 2435-2446. doi: 10.1101/gad.1340505.

[6]

Michael J. Quon and L. A. Campfield, A mathematical model and computer simulation study of insulin receptor regulation, J. Theor. Biol., 150 (1991), 59-72. doi: 10.1016/S0022-5193(05)80475-8.

[7]

Michael J. Quon and L. A. Campfield, A mathematical model and computer simulation study of insulin-sensitive glucose transporter regulation, J. Theor. Biol., 150 (1991), 93-107. doi: 10.1016/S0022-5193(05)80477-1.

[8]

Jaime Resino and Antonio García-Bellido, Drosophila genetic variants that change cell size and rate of proliferation affect cell communication and hence patterning, Mechanisms of Development, 121 (2004), 351-364. doi: 10.1016/j.mod.2004.02.007.

[9]

Ahmad R. Sedaghat, Arthur Sherman and Michael J. Quon, A mathematical model of metabolic insulin signaling pathways, Am. J. Physiol. Endocrinol. Metab., 283 (2002), 84-101.

[10]

Alexander W. Shingleton, The regulation of organ size in drosophila, Organogenesis, 6 (2010), 1-13.

[11]

Graham R. Smith and Daryl P. Shanley, Modelling the response of FOXO transcription factor to multiple post-translational modifications made by ageing-related signalling pathways, PLoS ONE, 5 (2010), 1-18. doi: 10.1371/journal.pone.0011092.

[12]

Huiyuan Tang, Martha S. B. Smith-Caldas, Michael V. Driscoll, Samy Salhadar and Alexander W. Shingleton, FOXO regulates organ-specific phenotypic plasticity in drosophila, PLoS Genet., 7 (2011), 1-12. doi: 10.1371/journal.pgen.1002373.

[13]

Lars P. Van Der Heide, Marco F. M. Hoekman and Marten P. Smidt, The ins and outs of FoxO shuttling: Mechanism of FoxO translocation and transcriptional regulation, Biochem. J., 380 (2004), 297-309.

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