ArticleDiabetes2014
Akt-dependent phosphorylation of hepatic FoxO1 is compartmentalized on a WD40/ProF scaffold and is selectively inhibited by aPKC in early phases of diet-induced obesity.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Miao Sour Soup Modulates Hepatic Gluconeogenesis Through PI3K/Akt/Foxo1 Signaling in High-Fat Diet-Induced Rats.Food science & nutrition · 2026Article
- Protein Kinase C Regulates Meiosis in Mammalian Oocytes.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Intracellular Sphingosine-1-Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Review
- Involvement of Transcription Factor FoxO1 in the Pathogenesis of Polycystic Ovary Syndrome.Frontiers in physiology · 2021Review
- Myosin IIB assembly state determines its mechanosensitive dynamics.The Journal of cell biology · 2019Article
- Insulin signaling and reduced glucocorticoid receptor activity attenuate postprandial gene expression in liver.PLoS biology · 2018Article
- Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism.Adipocyte · 2018Article
- Atypical PKC, PKCλ/ι, activates β-secretase and increases AβNeurobiology of aging · 2018Article
- A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.Nature communications · 2017Article
- Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis.International journal of oncology · 2017Article
- Biochemistry and neuroscience: the twain need to meet.Current opinion in neurobiology · 2017Review
- Targeting hepatic glucose metabolism in the treatment of type 2 diabetes.Nature reviews. Drug discovery · 2016Review
- Article
- Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.eLife · 2016Article
- Amino Acid-Induced Activation of mTORC1 in Rat Liver Is Attenuated by Short-Term Consumption of a High-Fat Diet.The Journal of nutrition · 2015Article
- BMI-related progression of atypical PKC-dependent aberrations in insulin signaling through IRS-1, Akt, FoxO1 and PGC-1α in livers of obese and type 2 diabetic humans.Metabolism: clinical and experimental · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Initiating mechanisms that impair gluconeogenic enzymes and spare lipogenic enzymes in diet-induced obesity (DIO) are obscure. Here, we examined insulin signaling to Akt and atypical protein kinase C (aPKC) in liver and muscle and hepatic enzyme expression in mice consuming a moderate high-fat (HF) diet. In HF diet-fed mice, resting/basal and insulin-stimulated Akt and aPKC activities were diminished in muscle, but in liver, these activities were elevated basally and were increased by insulin to normal levels. Despite elevated hepatic Akt activity, FoxO1 phosphorylation, which diminishes gluconeogenesis, was impaired; in contrast, Akt-dependent phosphorylation of glycogenic GSK3β and lipogenic mTOR was elevated. Diminished Akt-dependent FoxO1 phosphorylation was associated with reduced Akt activity associated with scaffold protein WD40/Propeller/FYVE (WD40/ProF), which reportedly facilitates FoxO1 phosphorylation. In contrast, aPKC activity associated with WD40/ProF was increased. Moreover, inhibition of hepatic aPKC reduced its association with WD40/ProF, restored WD40/ProF-associated Akt activity, restored FoxO1 phosphorylation, and corrected excessive expression of hepatic gluconeogenic and lipogenic enzymes. Additionally, Akt and aPKC activities in muscle improved, as did glucose intolerance, weight gain, hepatosteatosis, and hyperlipidemia. We conclude that Akt-dependent FoxO1 phosphorylation occurs on the WD/Propeller/FYVE scaffold in liver and is selectively inhibited in early DIO by diet-induced increases in activity of cocompartmentalized aPKC.
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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.