ArticleThe Journal of biological chemistry2016
Systems-wide Experimental and Modeling Analysis of Insulin Signaling through Forkhead Box Protein O1 (FOXO1) in Human Adipocytes, Normally and in Type 2 Diabetes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Blood Focused-Metabolomics and Transcriptomics Uncover Non-Linear Risk Association of Inadequate Dietary Choline Intake-Linked Metabolic Stress with MASLD Through Amino Acid Biomarkers,International journal of molecular sciences · 2026Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- Adipose tissue dysfunction disrupts metabolic homeostasis: mechanisms linking fat dysregulation to disease.Frontiers in endocrinology · 2025Review
- The Effect of Isotretinoin on Insulin Resistance and Serum Adiponectin Levels in Acne Vulgaris Patients: A Systematic Review and Meta-Analysis.Clinics and practice · 2024Review
- A comprehensive mechanistic model of adipocyte signaling with layers of confidence.NPJ systems biology and applications · 2023Article
- Digital twin predicting diet response before and after long-term fasting.PLoS computational biology · 2022Article
- mTOR: A Potential New Target in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Queueing theory model of mTOR complexes' impact on Akt-mediated adipocytes response to insulin.PloS one · 2022Article
- No evidence for change in expression ofAdipocyte · 2021Article
- 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
- Forkhead Box Protein O1: Functional Diversity and Post-Translational Modification, a New Therapeutic Target?Drug design, development and therapy · 2021Review
- An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow.Frontiers in physiology · 2021Article
- A systems biology analysis of lipolysis and fatty acid release from adipocytes in vitro and from adipose tissue in vivo.PloS one · 2021Article
- 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
- AKT/mTORC2 Inhibition Activates FOXO1 Function in CLL Cells Reducing B-Cell Receptor-Mediated Survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Whole Transcriptome Analysis of Obese Adipose Tissue Suggests u001kfc.1 as a Potential Regulator to Glucose Homeostasis.Frontiers in genetics · 2019Article
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin resistance is a major aspect of type 2 diabetes (T2D), which results from impaired insulin signaling in target cells. Signaling to regulate forkhead box protein O1 (FOXO1) may be the most important mechanism for insulin to control transcription. Despite this, little is known about how insulin regulates FOXO1 and how FOXO1 may contribute to insulin resistance in adipocytes, which are the most critical cell type in the development of insulin resistance. We report a detailed mechanistic analysis of insulin control of FOXO1 in human adipocytes obtained from non-diabetic subjects and from patients with T2D. We show that FOXO1 is mainly phosphorylated through mTORC2-mediated phosphorylation of protein kinase B at Ser(473) and that this mechanism is unperturbed in T2D. We also demonstrate a cross-talk from the MAPK branch of insulin signaling to stimulate phosphorylation of FOXO1. The cellular abundance and consequently activity of FOXO1 are halved in T2D. Interestingly, inhibition of mTORC1 with rapamycin reduces the abundance of FOXO1 to the levels in T2D. This suggests that the reduction of the concentration of FOXO1 is a consequence of attenuation of mTORC1, which defines much of the diabetic state in human adipocytes. We integrate insulin control of FOXO1 in a network-wide mathematical model of insulin signaling dynamics based on compatible data from human adipocytes. The diabetic state is network-wide explained by attenuation of an mTORC1-to-insulin receptor substrate-1 (IRS1) feedback and reduced abundances of insulin receptor, GLUT4, AS160, ribosomal protein S6, and FOXO1. The model demonstrates that attenuation of the mTORC1-to-IRS1 feedback is a major mechanism of insulin resistance in the diabetic state.
Indexed as
Identifiers
What OpenQuestion holds
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.