ArticleCell metabolism2014
Metabolic inflexibility impairs insulin secretion and results in MODY-like diabetes in triple FoxO-deficient mice.
Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 98 citations in OpenAlex.
- mNature metabolism · 2026Article
- Non-enzymatic hepatic ABHD6 interacts with Akt-FoxO1 axis to regulate metabolic health.Nature communications · 2026Article
- Investigational treatments of β-cell failure and replacement.Diabetology international · 2026Review
- Non-enzymatic ABHD6 interacts with Akt-FoxO1 axis to regulate selective hepatic insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- TSC22D1 is a newly identified inhibitor of insulin secretion in pancreatic beta cells.The FEBS journal · 2025Article
- Dynamic Ca2+-Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity.Diabetes · 2025Article
- Insulin resistance in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Endoplasmic reticulum stress and forkhead box protein O1 inhibition mediate palmitic acid and high glucose-induced β-cell dedifferentiation.World journal of diabetes · 2025Article
- β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects.The Journal of clinical endocrinology and metabolism · 2025Article
- CaFrontiers in endocrinology · 2024Review
- Cyb5r3 activation rescues secondary failure to sulfonylurea but not β-cell dedifferentiation.PloS one · 2024Article
- Metabolic and Genetic Association of Vitamin D with Calcium Signaling and Insulin Resistance.Indian journal of clinical biochemistry : IJCB · 2023Review
- Deletion of theInternational journal of molecular sciences · 2023Article
- Nutrient regulation of the islet epigenome controls adaptive insulin secretion.The Journal of clinical investigation · 2023Article
- A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes.Nature cell biology · 2023Article
- Review
- Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure.Nature communications · 2023Article
- Reflections on the state of diabetes research and prospects for treatment.Diabetology international · 2023Review
- High glucose impairs osteogenic differentiation of embryonic stem cells via early diversion of beta-catenin from Forkhead box O to T cell factor interaction.Birth defects research · 2022Article
- The Role of Forkhead Box O in Pathogenesis and Therapy of Diabetes Mellitus.International journal of molecular sciences · 2022Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Pancreatic β cell failure in type 2 diabetes is associated with functional abnormalities of insulin secretion and deficits of β cell mass. It's unclear how one begets the other. We have shown that loss of β cell mass can be ascribed to impaired FoxO1 function in different models of diabetes. Here we show that ablation of the three FoxO genes (1, 3a, and 4) in mature β cells results in early-onset, maturity-onset diabetes of the young (MODY)-like diabetes, with abnormalities of the MODY networks Hnf4α, Hnf1α, and Pdx1. FoxO-deficient β cells are metabolically inflexible, i.e., they preferentially utilize lipids rather than carbohydrates as an energy source. This results in impaired ATP generation and reduced Ca(2+)-dependent insulin secretion. The present findings demonstrate a secretory defect caused by impaired FoxO activity that antedates dedifferentiation. We propose that defects in both pancreatic β cell function and mass arise through FoxO-dependent mechanisms during diabetes progression.
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