ArticleEndocrinology2019
Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Article
- Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus.Nutrients · 2023Review
- Suppression of FOXO1 attenuates inflamm-aging and improves liver function during aging.Aging cell · 2023Article
- The Pathogenesis of Diabetes.International journal of molecular sciences · 2023Review
- Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats.Brain and behavior · 2023Article
- Fecal metabolomics combined with 16S rRNA gene sequencing to analyze the effect of Jiaotai pill intervention in type 2 diabetes mellitus rats.Frontiers in nutrition · 2023Article
- Article
- Role of Forkhead Box Protein O1 (FoxO1) in Stroke: A Literature Review.Aging and disease · 2022Review
- Insulin action at a molecular level - 100 years of progress.Molecular metabolism · 2021Review
- Crosstalk of Diabetic Conditions with Static Versus Dynamic Flow Environment-Impact on Aortic Valve Remodeling.International journal of molecular sciences · 2021Article
- Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.International journal of molecular sciences · 2021Review
- Alterations of Gut Microbiota by Overnutrition Impact Gluconeogenic Gene Expression and Insulin Signaling.International journal of molecular sciences · 2021Review
- Angiotensin II-upregulated MAP kinase phosphatase-3 modulates FOXO1 and p21 in adrenocortical H295R cells.Heliyon · 2020Article
- Perspectives on benefit of early and prereperfusion hypothermia by pharmacological approach in stroke.Brain circulationReview
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
The transcription factor forkhead box O1 (FoxO1) is a key mediator in the insulin signaling pathway and controls multiple physiological functions, including hepatic glucose production (HGP) and pancreatic β-cell function. We previously demonstrated that S256 in human FOXO1 (FOXO1-S256), equivalent to S253 in mouse FoxO1 (FoxO1-S253), is a key phosphorylation site mediating the effect of insulin as a target of protein kinase B on suppression of FOXO1 activity and expression of target genes responsible for gluconeogenesis. Here, we investigated the role of FoxO1-S253 phosphorylation in control of glucose homeostasis in vivo by generating global FoxO1-S253A/A knockin mice, in which FoxO1-S253 alleles were replaced with alanine (A substitution) blocking FoxO1-S253 phosphorylation. FoxO1-S253A/A mice displayed mild increases in feeding blood glucose and insulin levels but decreases in fasting blood glucose and glucagon concentrations, as well as a reduction in the ratio of pancreatic α-cells/β-cells per islet. FoxO1-S253A/A mice exhibited a slight increase in energy expenditure but barely altered food intake and glucose uptake among tissues. Further analyses revealed that FoxO1-S253A/A enhances FoxO1 nuclear localization and promotes the effect of glucagon on HGP. We conclude that dephosphorylation of S253 in FoxO1 may reflect a molecular basis of pancreatic plasticity during the development of insulin resistance.
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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.