Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus
Background : Major alteration in lifestyle of human population has promoted Type 2 diabetes mellitus (T2DM) to the level of an epidemic. This metabolic disorder is characterized by insulin resistance and pancreaticβ-cell dysfunction and apoptosis, triggered by endoplasmic reticulum (ER) stress, oxid...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/105995 http://hdl.handle.net/10220/48812 |
| _version_ | 1826116475111342080 |
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| author | Dutta, Pritha Ma, Lichun Ali, Yusuf Sloot, Peter M.A. Zheng, Jie |
| author2 | School of Computer Science and Engineering |
| author_facet | School of Computer Science and Engineering Dutta, Pritha Ma, Lichun Ali, Yusuf Sloot, Peter M.A. Zheng, Jie |
| author_sort | Dutta, Pritha |
| collection | NTU |
| description | Background : Major alteration in lifestyle of human population has promoted Type 2 diabetes mellitus (T2DM) to the level of an epidemic. This metabolic disorder is characterized by insulin resistance and pancreaticβ-cell dysfunction and apoptosis, triggered by endoplasmic reticulum (ER) stress, oxidative stress and cytokines. Computational modeling is necessary to consolidate information from various sources in order to obtain a comprehensive understanding of the pathogenesis of T2DM and to investigate possible interventions by performing in silico simulations. Results : In this paper, we propose a Boolean network model integrating the insulin resistance pathway with pancreatic β-cell apoptosis pathway which are responsible for T2DM. The model has five input signals, i.e. ER stress, oxidative stress, tumor necrosis factor α (TNFα), Fas ligand (FasL), and interleukin-6 (IL-6). We performed dynamical simulations using random order asynchronous update and with different combinations of the input signals. From the results, we observed that the proposed model made predictions that closely resemble the expression levels of genes in T2DM as reported in the literature. Conclusion : The proposed model can make predictions about expression levels of genes in T2DM that are in concordance with literature. Although experimental validation of the model is beyond the scope of this study, the model can be useful for understanding the aetiology of T2DM and discovery of therapeutic intervention for this prevalent complex disease. The files of our model and results are available at https://github.com/JieZheng-ShanghaiTech/boolean-t2dm. |
| first_indexed | 2024-10-01T04:12:20Z |
| format | Journal Article |
| id | ntu-10356/105995 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:12:20Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1059952020-11-01T04:44:41Z Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus Dutta, Pritha Ma, Lichun Ali, Yusuf Sloot, Peter M.A. Zheng, Jie School of Computer Science and Engineering Interdisciplinary Graduate School (IGS) Lee Kong Chian School of Medicine (LKCMedicine) Complexity Institute Boolean Model Type 2 Diabetes Mellitus DRNTU::Science::Medicine Background : Major alteration in lifestyle of human population has promoted Type 2 diabetes mellitus (T2DM) to the level of an epidemic. This metabolic disorder is characterized by insulin resistance and pancreaticβ-cell dysfunction and apoptosis, triggered by endoplasmic reticulum (ER) stress, oxidative stress and cytokines. Computational modeling is necessary to consolidate information from various sources in order to obtain a comprehensive understanding of the pathogenesis of T2DM and to investigate possible interventions by performing in silico simulations. Results : In this paper, we propose a Boolean network model integrating the insulin resistance pathway with pancreatic β-cell apoptosis pathway which are responsible for T2DM. The model has five input signals, i.e. ER stress, oxidative stress, tumor necrosis factor α (TNFα), Fas ligand (FasL), and interleukin-6 (IL-6). We performed dynamical simulations using random order asynchronous update and with different combinations of the input signals. From the results, we observed that the proposed model made predictions that closely resemble the expression levels of genes in T2DM as reported in the literature. Conclusion : The proposed model can make predictions about expression levels of genes in T2DM that are in concordance with literature. Although experimental validation of the model is beyond the scope of this study, the model can be useful for understanding the aetiology of T2DM and discovery of therapeutic intervention for this prevalent complex disease. The files of our model and results are available at https://github.com/JieZheng-ShanghaiTech/boolean-t2dm. MOE (Min. of Education, S’pore) Published version 2019-06-19T01:49:14Z 2019-12-06T22:02:29Z 2019-06-19T01:49:14Z 2019-12-06T22:02:29Z 2019 Journal Article Dutta, P., Ma, L., Ali, Y., Sloot, P. M. A., & Zheng, J. (2019). Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus. BMC Systems Biology, 13(S2), 36-. doi:10.1186/s12918-019-0692-0 https://hdl.handle.net/10356/105995 http://hdl.handle.net/10220/48812 10.1186/s12918-019-0692-0 en BMC Systems Biology © 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. 12 p. application/pdf |
| spellingShingle | Boolean Model Type 2 Diabetes Mellitus DRNTU::Science::Medicine Dutta, Pritha Ma, Lichun Ali, Yusuf Sloot, Peter M.A. Zheng, Jie Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| title | Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| title_full | Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| title_fullStr | Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| title_full_unstemmed | Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| title_short | Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| title_sort | boolean network modeling of β cell apoptosis and insulin resistance in type 2 diabetes mellitus |
| topic | Boolean Model Type 2 Diabetes Mellitus DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/105995 http://hdl.handle.net/10220/48812 |
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