ArticleDiabetologia2008
Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 98 citations in OpenAlex.
- Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals.Science advances · 2025Trial
- Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action.Diabetologia · 2010Trial
- Altered PI3-kinase/Akt signalling in skeletal muscle of young men with low birth weight.PloS one · 2008Trial
- A Novel Blend ofFoods (Basel, Switzerland) · 2026Article
- Tissue-Specific Enhancement of Insulin Function and Restoration of Glucose-Stimulated Insulin Secretion byPharmaceuticals (Basel, Switzerland) · 2025Article
- The dose-effect response of combined red and infrared photobiomodulation on insulin resistance in skeletal muscle cells.Biochemistry and biophysics reports · 2024Article
- Circadian Clock Desynchronization and Insulin Resistance.International journal of environmental research and public health · 2022Review
- PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.Cell communication and signaling : CCS · 2022Article
- iPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion.Stem cell research & therapy · 2022Article
- Discovering Tuberosin and Villosol as Potent and Selective Inhibitors of AKT1 for Therapeutic Targeting of Oral Squamous Cell Carcinoma.Journal of personalized medicine · 2022Article
- PHLPP1 promotes neutral lipid accumulation through AMPK/ChREBP-dependent lipid uptake and fatty acid synthesis pathways.iScience · 2022Article
- Mammalian AKT, the Emerging Roles on Mitochondrial Function in Diseases.Aging and disease · 2022Review
- PHLPP Signaling in Immune Cells.Current topics in microbiology and immunology · 2022Review
- AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance.Reviews in endocrine & metabolic disorders · 2021Review
- Role of Akt isoforms in neuronal insulin signaling and resistance.Cellular and molecular life sciences : CMLS · 2021Article
- Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes.World journal of biological chemistry · 2021Review
- Emerging roles of PHLPP phosphatases in metabolism.BMB reports · 2021Review
- Defining the underlying defect in insulin action in type 2 diabetes.Diabetologia · 2021Review
- AKT1 Regulates Endoplasmic Reticulum Stress and Mediates the Adaptive Response of Pancreatic β Cells.Molecular and cellular biology · 2020Article
- The Phosphatase PHLPP2 Plays a Key Role in the Regulation of Pancreatic Beta-Cell Survival.International journal of endocrinology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe serine/threonine kinase Akt/protein kinase B (PKB) is required for the metabolic actions of insulin. Controversial data have been reported regarding Akt defective activation in the muscle of type 2 diabetic patients. Because three Akt isoforms exist, each having a distinct physiological role, we investigated the contribution of isoform-specific defects to insulin signalling in human muscle.
methodsThe phosphorylation pattern and kinase activity of each Akt isoform were compared in primary myotubes from healthy control participants and type 2 diabetic patients. Phosphorylation of Ser(473) and of Thr(308) in each isoform was determined after immunoprecipitation in myotubes treated or not with insulin.
resultsMuscle cells from diabetic patients displayed defective insulin action and a drastic reduction of insulin-stimulated activity of all Akt isoforms. This was associated with specific defects of their phosphorylation pattern in response to insulin, with impaired Akt2- (and to a lower extent Akt3-) Ser(473) phosphorylation, and with altered Akt1-Thr(308) phosphorylation. These defects were not due to faulty phosphoinositide-dependent protein kinase 1 (PDK1) production or activation. Rather, we found higher levels of the Akt2-Ser(473)-specific protein phosphatase PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in muscle from diabetic patients, which may contribute to the alteration of Akt2-Ser(473) phosphorylation. CONCLUSIONS/
interpretationThese results suggest that several mechanisms affecting Akt isoforms, including deregulated production of PHLPP1, could underlie the alterations of skeletal muscle insulin signalling in type 2 diabetes. Taking into account the recently described isoform-specific metabolic functions of Akt, our results provide mechanistic insight that may contribute to the defective regulation of glucose and lipid metabolisms in the muscle of diabetic patients.
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