ArticleThe Journal of biological chemistry2012
Amplification and demultiplexing in insulin-regulated Akt protein kinase pathway in adipocytes.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- The insulin resistance mosaic: defect, defence or both? A perspective on what insulin resistance means and whether it should be treated.Diabetologia · 2026Article
- 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
- Akt may associate with insulin-responsive vesicles via interaction with sortilin.FEBS letters · 2024Article
- PKCα Isoform Inhibits Insulin Signaling and Aggravates Neuronal Insulin Resistance.Molecular neurobiology · 2023Article
- Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance.Nature communications · 2023Article
- Integrating adipocyte insulin signaling and metabolism in the multi-omics era.Trends in biochemical sciences · 2022Review
- The aetiology and molecular landscape of insulin resistance.Nature reviews. Molecular cell biology · 2021Review
- Signaling Heterogeneity is Defined by Pathway Architecture and Intercellular Variability in Protein Expression.iScience · 2021Article
- Maternal exercise attenuates the lower skeletal muscle glucose uptake and insulin secretion caused by paternal obesity in female adult rat offspring.The Journal of physiology · 2020Article
- Gamma radiation improves AD pathogenesis in APP/PS1 mouse model by potentiating insulin sensitivity.Heliyon · 2020Article
- Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes.The Journal of biological chemistry · 2019Article
- Muscle and adipose tissue insulin resistance: malady without mechanism?Journal of lipid research · 2019Review
- Crosstalk in transition: the translocation of Akt.Journal of mathematical biology · 2019Article
- Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by a paternal high-fat diet.The Journal of physiology · 2019Article
- Phosphorylation-Dependent Inhibition of Akt1.Genes · 2018Article
- Sphingolipid changes do not underlie fatty acid-evoked GLUT4 insulin resistance nor inflammation signals in muscle cells.Journal of lipid research · 2018Article
- Rac1 muscle knockout exacerbates the detrimental effect of high-fat diet on insulin-stimulated muscle glucose uptake independently of Akt.The Journal of physiology · 2018Article
- Tankyrase modulates insulin sensitivity in skeletal muscle cells by regulating the stability of GLUT4 vesicle proteins.The Journal of biological chemistry · 2018Article
- Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding.Journal of molecular endocrinology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Akt plays a major role in insulin regulation of metabolism in muscle, fat, and liver. Here, we show that in 3T3-L1 adipocytes, Akt operates optimally over a limited dynamic range. This indicates that Akt is a highly sensitive amplification step in the pathway. With robust insulin stimulation, substantial changes in Akt phosphorylation using either pharmacologic or genetic manipulations had relatively little effect on Akt activity. By integrating these data we observed that half-maximal Akt activity was achieved at a threshold level of Akt phosphorylation corresponding to 5-22% of its full dynamic range. This behavior was also associated with lack of concordance or demultiplexing in the behavior of downstream components. Most notably, FoxO1 phosphorylation was more sensitive to insulin and did not exhibit a change in its rate of phosphorylation between 1 and 100 nm insulin compared with other substrates (AS160, TSC2, GSK3). Similar differences were observed between various insulin-regulated pathways such as GLUT4 translocation and protein synthesis. These data indicate that Akt itself is a major amplification switch in the insulin signaling pathway and that features of the pathway enable the insulin signal to be split or demultiplexed into discrete outputs. This has important implications for the role of this pathway in disease.
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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.