ArticleThe Journal of clinical investigation2000
Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 351 papers, 2 of them syntheses that pooled it.
What it found
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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
351 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,129 citations in OpenAlex.
- Adipose Tissue Dysfunction in Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2023Pooled it
- Pooled it
- High-intensity interval training combining rowing and cycling efficiently improves insulin sensitivity, body composition and VOFrontiers in endocrinology · 2022Trial
- Trial
- Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans.Scientific reports · 2021 · on this mapTrial
- The effect of muraglitazar on adiponectin signalling, mitochondrial function and fat oxidation genes in human skeletal muscle in vivo.Diabetic medicine : a journal of the British Diabetic Association · 2015Trial
- Gene and MicroRNA Expression Responses to Exercise; Relationship with Insulin Sensitivity.PloS one · 2015Trial
- A single mechanism can explain network-wide insulin resistance in adipocytes from obese patients with type 2 diabetes.The Journal of biological chemistry · 2014Trial
- One bout of exercise alters free-living postprandial glycemia in type 2 diabetes.Medicine and science in sports and exercise · 2014Trial
- Trial
- Aerobic and combined exercise sessions reduce glucose variability in type 2 diabetes: crossover randomized trial.PloS one · 2013Trial
- Association of insulin resistance indices with major adverse cardiovascular events in patients with acute myocardial infarction and chronic Kidney disease: a retrospective cohort study.Annals of medicine · 2026Article
- Curcumol Alleviates Obesity-Related Insulin Resistance and Inflammation in Skeletal Muscle via the SRC/PI3K/AKT Axis.Nutrients · 2026Article
- Combined associations of the metabolic score for insulin resistance and estimated glucose disposal rate with cardio-renal-metabolic multimorbidity: evidence from two large population studies.BMC cardiovascular disorders · 2026Article
- The Association between Sarcopenia and Chronic Kidney Disease among the Patients of Diabetes Mellitus: Korean National Health and Nutrition Examination Survey 2008-2011.Journal of bone metabolism · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Feeding the invaders: how metabolic imbalance shapes infection and biofilm development.FEMS microbiology reviews · 2026Review
- The role of PYY in improving insulin resistance.Frontiers in endocrinology · 2026Review
- Review
- Vegan and Plant-Based Diets in the Management of Metabolic Syndrome: A Narrative Review from Anti-Inflammatory and Antithrombotic Perspectives.Nutrients · 2025Review
291 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The broad nature of insulin resistant glucose metabolism in skeletal muscle of patients with type 2 diabetes suggests a defect in the proximal part of the insulin signaling network. We sought to identify the pathways compromised in insulin resistance and to test the effect of moderate exercise on whole-body and cellular insulin action. We conducted euglycemic clamps and muscle biopsies on type 2 diabetic patients, obese nondiabetics and lean controls, with and without a single bout of exercise. Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance.
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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.