ArticleJournal of molecular medicine (Berlin, Germany)2013
Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism.
Article in Journal of molecular medicine (Berlin, Germany), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies.JCI insight · 2026Article
- A direct effect of the hematocrit on blood glucose: Evidence from hypoxia- and erythropoietin-treated mice.Science advances · 2025Article
- Control of NADThe EMBO journal · 2024Article
- Hypoxia-Induced Signaling in Gut and Liver Pathobiology.Annual review of pathology · 2024Review
- Increased transferrin protects from thrombosis in Chuvash erythrocytosis.American journal of hematology · 2023Article
- Iron and the Pathophysiology of Diabetes.Annual review of physiology · 2023Review
- [A case of familial erythrocytosis type 2 caused by VHL gene mutation].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2020Article
- Hypoxia-inducible factors and diabetes.The Journal of clinical investigation · 2020Review
- Interpretation of maternal blood glucose during pregnancy at high altitude area, Abha-Saudi Arabia.Journal of family medicine and primary care · 2020Article
- Diabetic atherosclerosis: is there a role for the hypoxia-inducible factors?Bioscience reports · 2020Review
- Changes in expression of genes related to glucose metabolism in liver and skeletal muscle of rats exposed to acute hypoxia.Heliyon · 2020Article
- Thrombotic risk in congenital erythrocytosis due to up-regulated hypoxia sensing is not associated with elevated hematocrit.Haematologica · 2020Article
- Metabonomics window into plateau hypoxia.The Journal of international medical research · 2019Review
- Re-evaluation of hematocrit as a determinant of thrombotic risk in erythrocytosis.Haematologica · 2019Review
- Unilateral digital arterial ligation combined with low molecular weight heparins in severed finger without venous anastomosis.Experimental and therapeutic medicine · 2018Article
- Role of Hypoxia-Inducible Factors 1α (HIF1α) in SH-SY5Y Cell Autophagy Induced by Oxygen-Glucose Deprivation.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.Cell metabolism · 2018Article
- RASAL1 inhibits HepG2 cell growth via HIF-2α mediated gluconeogenesis.Oncology letters · 2017Article
- Elevated pentose phosphate pathway is involved in the recovery of hypoxia‑induced erythrocytosis.Molecular medicine reports · 2017Article
- Metabolic basis to Sherpa altitude adaptation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia-inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzyme genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHL ( R200W ) homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wild-type VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHL ( R200W ) homozygotes. We expanded these observations in VHL ( R200W ) homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc, but not Pdk2, was decreased, and skeletal muscle expression of Glut1, Pdk1, and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients.
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