Boolean network modeling of -cell apoptosis and insulin resistance in type 2 diabetes mellitus

doi:10.1186/s12918-019-0692-0

	Boolean network modeling of -cell apoptosis and insulin resistance in type 2 diabetes mellitus
	Dutta, Pritha 1; Ma, Lichun 2; Ali, Yusuf 3; Sloot, Peter M. A.4; Zheng, Jie5
	2019-04-05
发表期刊	BMC SYSTEMS BIOLOGY
ISSN	1752-0509
卷号	13
发表状态	已发表
DOI	10.1186/s12918-019-0692-0
摘要	BackgroundMajor 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 pancreatic -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.ResultsIn this paper, we propose a Boolean network model integrating the insulin resistance pathway with pancreatic -cell apoptosis pathway which are responsible for T2DM. The model has five input signals, i.e. ER stress, oxidative stress, tumor necrosis factor (TNF ), 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.ConclusionThe 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.
关键词	Boolean model Type 2 diabetes mellitus Insulin resistance -cell apoptosis
收录类别	SCI ; SCIE ; CPCI
语种	英语
资助项目	Ministry of Education, Singapore[2015-T1-002-094]
WOS研究方向	Mathematical & Computational Biology
WOS类目	Mathematical & Computational Biology
WOS记录号	WOS:000463771600003
出版者	BMC
WOS关键词	ENDOPLASMIC-RETICULUM STRESS ; TUMOR-NECROSIS-FACTOR ; PANCREATIC BETA-CELLS ; SIGNAL-TRANSDUCTION ; OXIDATIVE STRESS ; SKELETAL-MUSCLE ; ACTIVATION ; KINASE ; DEATH ; ER
原始文献类型	Article ; Proceedings Paper
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/34278
专题	信息科学与技术学院信息科学与技术学院_PI研究组_郑杰组
通讯作者	Zheng, Jie
作者单位	1.Nanyang Techn Univ, Interdisciplinary Grad Sch, Singapore, Singapore 2.Nanyang Technol Univ, Sch Comp Sci & Engn, Biomed Informat Lab, Singapore, Singapore 3.Nanyang Techn Univ, Lee Kong Chian Sch Med, Singapore, Singapore 4.Nanyang Techn Univ, Complex Inst, Singapore, Singapore 5.ShanghaiTech Univ, Sch Informat Sci & Technol, Shanghai, Peoples R China
通讯作者单位	信息科学与技术学院
推荐引用方式 GB/T 7714	Dutta, Pritha,Ma, Lichun,Ali, Yusuf,et al. Boolean network modeling of -cell apoptosis and insulin resistance in type 2 diabetes mellitus[J]. BMC SYSTEMS BIOLOGY,2019,13.
APA	Dutta, Pritha,Ma, Lichun,Ali, Yusuf,Sloot, Peter M. A.,&Zheng, Jie.(2019).Boolean network modeling of -cell apoptosis and insulin resistance in type 2 diabetes mellitus.BMC SYSTEMS BIOLOGY,13.
MLA	Dutta, Pritha,et al."Boolean network modeling of -cell apoptosis and insulin resistance in type 2 diabetes mellitus".BMC SYSTEMS BIOLOGY 13(2019).