Evidence map›Paper›PMID 25029527›Full record

ArticlePloS one2014

Multi-tissue computational modeling analyzes pathophysiology of type 2 diabetes in MKR mice.

Amit Kumar, Thomas Harrelson, Nathan E Lewis, Emily J Gallagher, Derek LeRoith, Joseph Shiloach, Michael J Betenbaugh

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021
    Pooled it
  2. Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies.International journal of molecular sciences · 2025
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Metabolic network modeling with model organisms.Current opinion in chemical biology · 2017
    Review
  8. Article
  9. Review
  10. Constraint Based Modeling Going Multicellular.Frontiers in molecular biosciences · 2016
    Review
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Amit KumarDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America; Biotechnology Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, United States of America.
Thomas HarrelsonDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Nathan E LewisDepartment of Biology, Brigham Young University, Provo, Utah, United States of America.
Emily J GallagherDivision of Endocrinology, Diabetes and Bone Disease and the Diabetes, Obesity, Metabolism Institute, Icahn School of Medicine at Sinai, New York, New York, United States of America.
Derek LeRoithDivision of Endocrinology, Diabetes and Bone Disease and the Diabetes, Obesity, Metabolism Institute, Icahn School of Medicine at Sinai, New York, New York, United States of America.
Joseph ShiloachBiotechnology Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, United States of America.
Michael J BetenbaughDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
Johns Hopkins University · USIcahn School of Medicine at Mount Sinai · USBrigham Young University · USNational Institute of Diabetes and Digestive and Kidney Diseases · US

Funding

JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI AHIMA, REXFORD S. · 2013 to 2017
$9.7M
Identification of genes related to spcific properties of mammalian cellsZIADK075080 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI SHILOACH, JOSEPH · 2012 to 2022
$5.0M
Beta-cell ProliferationR01DK081472 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI HUSSAIN, MEHBOOB A, WONDISFORD, FREDRIC E. · 2009 to 2013
$2.1M
Intramural NIH HHSNIDDK NIH HHS P30 DK079637NIDDK NIH HHS R01 DK081472
6 · The paper itself

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.

Indexed as

AlgorithmsDisease Models, AnimalModels, BiologicalAdipose TissueAmino AcidsAnimalsComputer SimulationDiabetes Mellitus, Type 2Fatty AcidsGene Expression RegulationLiverMetabolic Flux AnalysisMetabolic Networks and PathwaysMiceMice, TransgenicMicroarray AnalysisAmino AcidsFatty AcidsIGF1R protein, humanReceptor, IGF Type 1Receptors, Somatomedin

Identifiers

PMID25029527
PMCPMC4100879
OpenAlexW2059986808

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.