ArticlePloS one2014
Multi-tissue computational modeling analyzes pathophysiology of type 2 diabetes in MKR mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021Pooled it
- Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Genome-scale metabolic models applied for human health and biopharmaceutical engineering.Quantitative biology (Beijing, China) · 2023Review
- Guidelines for extracting biologically relevant context-specific metabolic models using gene expression data.Metabolic engineering · 2023Article
- Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions.PLoS computational biology · 2019Article
- Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat.Scientific reports · 2018Article
- Metabolic network modeling with model organisms.Current opinion in chemical biology · 2017Review
- Reconstruction of Tissue-Specific Metabolic Networks Using CORDA.PLoS computational biology · 2016Article
- Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling.Frontiers in cardiovascular medicine · 2016Review
- Constraint Based Modeling Going Multicellular.Frontiers in molecular biosciences · 2016Review
- The beta-3 adrenergic agonist (CL-316,243) restores the expression of down-regulated fatty acid oxidation genes in type 2 diabetic mice.Nutrition & metabolism · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Computational models using metabolic reconstructions for in silico simulation of metabolic disorders such as type 2 diabetes mellitus (T2DM) can provide a better understanding of disease pathophysiology and avoid high experimentation costs. There is a limited amount of computational work, using metabolic reconstructions, performed in this field for the better understanding of T2DM. In this study, a new algorithm for generating tissue-specific metabolic models is presented, along with the resulting multi-confidence level (MCL) multi-tissue model. The effect of T2DM on liver, muscle, and fat in MKR mice was first studied by microarray analysis and subsequently the changes in gene expression of frank T2DM MKR mice versus healthy mice were applied to the multi-tissue model to test the effect. Using the first multi-tissue genome-scale model of all metabolic pathways in T2DM, we found out that branched-chain amino acids' degradation and fatty acids oxidation pathway is downregulated in T2DM MKR mice. Microarray data showed low expression of genes in MKR mice versus healthy mice in the degradation of branched-chain amino acids and fatty-acid oxidation pathways. In addition, the flux balance analysis using the MCL multi-tissue model showed that the degradation pathways of branched-chain amino acid and fatty acid oxidation were significantly downregulated in MKR mice versus healthy mice. Validation of the model was performed using data derived from the literature regarding T2DM. Microarray data was used in conjunction with the model to predict fluxes of various other metabolic pathways in the T2DM mouse model and alterations in a number of pathways were detected. The Type 2 Diabetes MCL multi-tissue model may explain the high level of branched-chain amino acids and free fatty acids in plasma of Type 2 Diabetic subjects from a metabolic fluxes perspective.
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