ArticleProceedings of the National Academy of Sciences of the United States of America2016
Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- miRNAs as cell-intrinsic epigenetic regulators in muscle in type 2 diabetes.Signal transduction and targeted therapy · 2026Article
- Review
- Non-linear association between metabolic score for insulin resistance and diabetes mellitus in normal-weight middle-aged and older Chinese adults: a multicenter retrospective cohort study.Frontiers in nutrition · 2025Article
- Organoids: their emerging essential role in pathological mechanisms and drug discovery of diabetes and its complications.Frontiers in pharmacology · 2025Review
- Organoid-guided precision hepatology for metabolic liver disease.Journal of hepatology · 2024Review
- Interactions among insulin resistance, epigenetics, and donor sex in gene expression regulation of iPSC-derived myoblasts.The Journal of clinical investigation · 2024Article
- Induced Pluripotent Stem Cells for Tissue-Engineered Skeletal Muscles.International journal of molecular sciences · 2023Review
- Activation of PDGF Signaling in the Adult Muscle Stem Cell Niche in Patients With Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2023Article
- Towards a better understanding of diabetes mellitus using organoid models.Nature reviews. Endocrinology · 2023Review
- Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models.Metabolites · 2022Review
- Review
- iPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion.Stem cell research & therapy · 2022Article
- Human Tissue-Engineered Skeletal Muscle: A Tool for Metabolic Research.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Stem Cell-Derived Islets for Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges.NPJ Regenerative medicine · 2022Review
- Deprogram and reprogram to solve the riddle of insulin resistance.The Journal of clinical investigation · 2021Article
- Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex.The Journal of clinical investigation · 2021Article
- Defining the underlying defect in insulin action in type 2 diabetes.Diabetologia · 2021Review
- Insulin resistance in diabetes: The promise of using induced pluripotent stem cell technology.World journal of stem cells · 2021Review
- Modeling different types of diabetes using human pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Induced pluripotent stem cells (iPS cells) represent a unique tool for the study of the pathophysiology of human disease, because these cells can be differentiated into multiple cell types in vitro and used to generate patient- and tissue-specific disease models. Given the critical role for skeletal muscle insulin resistance in whole-body glucose metabolism and type 2 diabetes, we have created a novel cellular model of human muscle insulin resistance by differentiating iPS cells from individuals with mutations in the insulin receptor (IR-Mut) into functional myotubes and characterizing their response to insulin in comparison with controls. Morphologically, IR-Mut cells differentiated normally, but had delayed expression of some muscle differentiation-related genes. Most importantly, whereas control iPS-derived myotubes exhibited in vitro responses similar to primary differentiated human myoblasts, IR-Mut myotubes demonstrated severe impairment in insulin signaling and insulin-stimulated 2-deoxyglucose uptake and glycogen synthesis. Transcriptional regulation was also perturbed in IR-Mut myotubes with reduced insulin-stimulated expression of metabolic and early growth response genes. Thus, iPS-derived myotubes from individuals with genetically determined insulin resistance demonstrate many of the defects observed in vivo in insulin-resistant skeletal muscle and provide a new model to analyze the molecular impact of muscle 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.