ArticleDiabetes2013
Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Bidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c.Journal of nanobiotechnology · 2025Article
- Deficiency of Ugcg in LSECs alleviates high-fat diet-induced MASLD.Hepatology communications · 2025Article
- State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer's Disease.Aging and disease · 2024Review
- Role of insulin action in the pathogenesis of diabetic complications.Diabetology international · 2022Review
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- New aspects of hepatic endothelial cells in physiology and nonalcoholic fatty liver disease.American journal of physiology. Cell physiology · 2020Review
- A fluorescent reporter assay of differential gene expression response to insulin in hepatocytes.American journal of physiology. Cell physiology · 2019Article
- Hallmarks of Aging in the Liver.Computational and structural biotechnology journal · 2019Review
- Insulin Action Research and the Future of Diabetes Treatment: The 2017 Banting Medal for Scientific Achievement Lecture.Diabetes · 2018Article
- Emerging Roles of Vascular Endothelium in Metabolic Homeostasis.Circulation research · 2018Review
- Biochemical and cellular properties of insulin receptor signalling.Nature reviews. Molecular cell biology · 2018Review
- Endothelial Cell Metabolism.Physiological reviews · 2018Review
- Forkhead box class O family member proteins: The biology and pathophysiological roles in diabetes.Journal of diabetes investigation · 2017Review
- Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin's glucose-lowering effects.Science translational medicine · 2017Article
- Antifibrotic effect of pirfenidone in a mouse model of human nonalcoholic steatohepatitis.Scientific reports · 2017Article
- Synthesis of substituted 2MedChemComm · 2017Article
- MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue.Circulation research · 2016Article
- Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice.Journal of inherited metabolic disease · 2016Article
- The new biology of diabetes.Diabetologia · 2015Review
- Reduced hepatic eNOS phosphorylation is associated with NAFLD and type 2 diabetes progression and is prevented by daily exercise in hyperphagic OLETF rats.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Insulin signaling in vascular endothelial cells (ECs) is critical to maintain endothelial function but also to mediate insulin action on peripheral glucose disposal. However, gene knockout studies have reached disparate conclusions. Thus, insulin receptor inactivation in ECs does not impair insulin action, whereas inactivation of Irs2 does. Previously, we have shown that endothelial ablation of the three Foxo genes protects mice from atherosclerosis. Interestingly, here we show that mice lacking FoxO isoforms in ECs develop hepatic insulin resistance through excessive generation of nitric oxide (NO) that impairs insulin action in hepatocytes via tyrosine nitration of insulin receptors. Coculture experiments demonstrate that NO produced in liver sinusoidal ECs impairs insulin's ability to suppress glucose production in hepatocytes. The effects of liver sinusoidal ECs can be mimicked by NO donors and can be reversed by NO inhibitors in vivo and ex vivo. The findings are consistent with a model in which excessive, rather than reduced, insulin signaling in ECs predisposes to systemic insulin resistance, prompting a reevaluation of current approaches to insulin sensitization.
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What OpenQuestion holds
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.