ArticleDiabetologia2013
Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02017210 (Insulin-sensitive Obesity), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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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.
Insulin-sensitive Obesity: Prospective and Interventional Studies
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Baicalin and its aglycone: a novel approach for treatment of metabolic disorders.Pharmacological reports : PR · 2020Pooled it
- DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation.EMBO reports · 2026Article
- Sinapine Modulates Glycogen and Lipid Synthesis via IRS1-PI3K-AKT-GSK3β-GS Pathway in Insulin-Resistant Models.Food science & nutrition · 2026Article
- Effect of lithium on glucose homeostasis: Role of protein kinase B (AKT) in rats.Open veterinary journal · 2025Article
- Tissue-Specific Enhancement of Insulin Function and Restoration of Glucose-Stimulated Insulin Secretion byPharmaceuticals (Basel, Switzerland) · 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
- Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise.Circulation research · 2025Review
- NPC86 Increases LncRNA Gas5 In Vivo to Improve Insulin Sensitivity and Metabolic Function in Diet-Induced Obese Diabetic Mouse Model.International journal of molecular sciences · 2025Article
- Pharmacological advances in multi-targeted strategies for type 2 diabetes mellitus: a systematic perspective based on traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- The dose-effect response of combined red and infrared photobiomodulation on insulin resistance in skeletal muscle cells.Biochemistry and biophysics reports · 2024Article
- Qinlian Hongqu Decoction Modulates FXR/TGR5/GLP-1 Pathway to Improve Insulin Resistance in NAFLD Mice: Bioinformatics and Experimental Study.ACS omega · 2024Article
- Article
- Impact of Sex on the Therapeutic Efficacy of Rosiglitazone in Modulating White Adipose Tissue Function and Insulin Sensitivity.Nutrients · 2024Article
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- Article
- Basal autophagic flux measured in blood correlates positively with age in adults at increased risk of type 2 diabetes.GeroScience · 2023Observational
- Endothelin-1 in Health and Disease.International journal of molecular sciences · 2023Review
- Insulin signalling and GLUT4 trafficking in insulin resistance.Biochemical Society transactions · 2023Review
- CHIP Haploinsufficiency Exacerbates Hepatic Steatosis via Enhanced TXNIP Expression and Endoplasmic Reticulum Stress Responses.Antioxidants (Basel, Switzerland) · 2023Article
5 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
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisMuscle insulin resistance, one of the earliest defects associated with type 2 diabetes, involves changes in the phosphoinositide 3-kinase/Akt network. The relative contribution of obesity vs insulin resistance to perturbations in this pathway is poorly understood.
methodsWe used phosphospecific antibodies against targets in the Akt signalling network to study insulin action in muscle from lean, overweight/obese and type 2 diabetic individuals before and during a hyperinsulinaemic-euglycaemic clamp.
resultsInsulin-stimulated Akt phosphorylation at Thr309 and Ser474 was highly correlated with whole-body insulin sensitivity. In contrast, impaired phosphorylation of Akt substrate of 160 kDa (AS160; also known as TBC1D4) was associated with adiposity, but not insulin sensitivity. Neither insulin sensitivity nor obesity was associated with defective insulin-dependent phosphorylation of forkhead box O (FOXO) transcription factor. In view of the resultant basal hyperinsulinaemia, we predicted that this selective response within the Akt pathway might lead to hyperactivation of those processes that were spared. Indeed, the expression of genes targeted by FOXO was downregulated in insulin-resistant individuals. CONCLUSIONS/
interpretationThese results highlight non-linearity in Akt signalling and suggest that: (1) the pathway from Akt to glucose transport is complex; and (2) pathways, particularly FOXO, that are not insulin-resistant, are likely to be hyperactivated in response to hyperinsulinaemia. This facet of Akt signalling may contribute to multiple features of the metabolic syndrome.
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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.