ArticleThe Journal of clinical investigation2021
Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- miRNAs as cell-intrinsic epigenetic regulators in muscle in type 2 diabetes.Signal transduction and targeted therapy · 2026Article
- Sexual identity of Akh neurons shapes Nucb1-dependent metabolic and reproductive plasticity.iScience · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Profiling Peripheral Blood with an Optimized, Multiplexed, Single-cell Multiome Approach Supports an Insulin-driven Asthma Subtype.bioRxiv : the preprint server for biology · 2026Article
- Phosphoproteomics of aged insulin-resistant bone identifies P70S6K phosphorylation of AFF4 as a gene-specific transcriptional regulator.Nature communications · 2025Article
- The insulin signalling network.Nature metabolism · 2025Review
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- Cellular composition and transcriptomics of subcutaneous adipose tissue linked to blood glycated haemoglobin.European journal of clinical investigation · 2025Article
- Skeletal muscle proteomics: considerations and opportunities.npj metabolic health and disease · 2025Review
- Single Herbal Medicine for Insulin Resistance: Protocol for a Systematic Review and Meta-Analysis of Randomized Clinical Trials.JMIR research protocols · 2025Article
- On the utility of immobilized phenylarsine oxide in the study of redox sensitive cardiac proteins.Scientific reports · 2025Article
- Cell-intrinsic insulin signaling defects in human iPS cell-derived hepatocytes in type 2 diabetes.The Journal of clinical investigation · 2025Article
- Sex differences in skeletal muscle metabolism in exercise and type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Article
- Insulin resistance unraveled: Hormonal correlations in gestational diabetes.Journal of medical biochemistry · 2024Article
- Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin.Cell reports · 2024Article
- Article
- Interactions among insulin resistance, epigenetics, and donor sex in gene expression regulation of iPSC-derived myoblasts.The Journal of clinical investigation · 2024Article
- Sex differences in energy metabolism: natural selection, mechanisms and consequences.Nature reviews. Nephrology · 2024Review
- NEFA Dynamics in Adults With Severe Obesity and Insulin Resistance: No Coupling to the rs9939609Journal of the Endocrine Society · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro. Integrating these data with data from type 2 diabetic iMyos revealed critical sites of conserved altered phosphorylation in IRS-1, AKT, mTOR, and TBC1D1 in addition to changes in protein phosphorylation involved in Rho/Rac signaling, chromatin organization, and RNA processing. There were also striking differences in the phosphoproteome in cells from men versus women. These sex-specific and insulin-resistance defects were linked to functional differences in downstream actions. Thus, there are cell-autonomous signaling alterations associated with insulin resistance within the general population and important differences between men and women, many of which also occur in diabetes, that contribute to differences in physiology and disease.
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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.