Trial reportThe Journal of biological chemistry2014
A single mechanism can explain network-wide insulin resistance in adipocytes from obese patients with type 2 diabetes.
Trial report in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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.
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Who cites it
26 citing papers in PubMed, 65 citations in OpenAlex.
- Microarray Analysis of Visceral Adipose Tissue in Obese Women Reveals Common Crossroads Among Inflammation, Metabolism, Addictive Behaviors, and Cancer: AKT3 and MAPK1 Cross Point in Obesity.Journal of obesity · 2024Article
- A multi-scale digital twin for adiposity-driven insulin resistance in humans: diet and drug effects.Diabetology & metabolic syndrome · 2023Article
- A comprehensive mechanistic model of adipocyte signaling with layers of confidence.NPJ systems biology and applications · 2023Article
- Insulin Signaling Pathway Model in Adipocyte Cells.Current pharmaceutical design · 2023Article
- Digital twin predicting diet response before and after long-term fasting.PLoS computational biology · 2022Article
- Dynamic modelling of the PI3K/MTOR signalling network uncovers biphasic dependence of mTORC1 activity on the mTORC2 subunit SIN1.PLoS computational biology · 2021Article
- Finding new edges: systems approaches to MTOR signaling.Biochemical Society transactions · 2021Review
- A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo.PloS one · 2021Article
- An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow.Frontiers in physiology · 2021Article
- Hybrid modelling for stroke care: Review and suggestions of new approaches for risk assessment and simulation of scenarios.NeuroImage. Clinical · 2021Review
- Perturbation biology links temporal protein changes to drug responses in a melanoma cell line.PLoS computational biology · 2020Article
- Pediatric Extrapolation in Type 2 Diabetes: Future Implications of a Workshop.Clinical pharmacology and therapeutics · 2020Article
- Computational Analysis of Insulin-Glucagon Signalling Network: Implications of Bistability to Metabolic Homeostasis and Disease states.Scientific reports · 2019Article
- Insulin and β-adrenergic receptors mediate lipolytic and anti-lipolytic signalling that is not altered by type 2 diabetes in human adipocytes.The Biochemical journal · 2019Article
- Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches.Epigenetics · 2018Article
- A closed-loop multi-level model of glucose homeostasis.PloS one · 2018Article
- Mathematical modeling of white adipocyte exocytosis predicts adiponectin secretion and quantifies the rates of vesicle exo- and endocytosis.The Journal of biological chemistry · 2017Article
- A systems biology analysis connects insulin receptor signaling with glucose transporter translocation in rat adipocytes.The Journal of biological chemistry · 2017Article
- Cross-talks via mTORC2 can explain enhanced activation in response to insulin in diabetic patients.Bioscience reports · 2017Article
- Systems biology reveals uncoupling beyond UCP1 in human white fat-derived beige adipocytes.NPJ systems biology and applications · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The response to insulin is impaired in type 2 diabetes. Much information is available about insulin signaling, but understanding of the cellular mechanisms causing impaired signaling and insulin resistance is hampered by fragmented data, mainly obtained from different cell lines and animals. We have collected quantitative and systems-wide dynamic data on insulin signaling in primary adipocytes and compared cells isolated from healthy and diabetic individuals. Mathematical modeling and experimental verification identified mechanisms of insulin control of the MAPKs ERK1/2. We found that in human adipocytes, insulin stimulates phosphorylation of the ribosomal protein S6 and hence protein synthesis about equally via ERK1/2 and mTORC1. Using mathematical modeling, we examined the signaling network as a whole and show that a single mechanism can explain the insulin resistance of type 2 diabetes throughout the network, involving signaling both through IRS1, PKB, and mTOR and via ERK1/2 to the nuclear transcription factor Elk1. The most important part of the insulin resistance mechanism is an attenuated feedback from the protein kinase mTORC1 to IRS1, which spreads signal attenuation to all parts of the insulin signaling network. Experimental inhibition of mTORC1 using rapamycin in adipocytes from non-diabetic individuals induced and thus confirmed the predicted network-wide insulin resistance.
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Registered trials
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.