ArticleThe Journal of clinical investigation2009
Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Peripheral blood HIF-1α levels in type 2 diabetes mellitus and their association with diabetic complications: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Transient Overexpression of pVHL Mediated by Adenoviral Vector Injection in Pancreatic Tissue Decreases Blood Glucose Levels in a Hypercaloric Diet-Induced Mouse Model of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2026Article
- Review
- Crosstalk between the aryl hydrocarbon receptor and hypoxia-inducible factor 1α pathways in human islet models.Islets · 2025Article
- Pseudohypoxia caused by germline genetic alterations in the VHL gene is associated with increased diabetes and cardiovascular risk: a UK biobank study.Cardiovascular diabetology · 2025Article
- Regulating islet stress responses through CD47 activation.Diabetologia · 2025Article
- Nicotinamide Mononucleotide (NMN) Ameliorates Free Fatty Acid-Induced Pancreatic β-Cell Dysfunction via the NADInternational journal of molecular sciences · 2024Article
- HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.Science translational medicine · 2024Article
- Biological hypoxia in pre-transplant human pancreatic islets induces transplant failure in diabetic mice.Scientific reports · 2024Article
- Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Adipose Tissue Hypoxia in Obesity: Clinical Reappraisal of Hypoxia Hypothesis.Advances in experimental medicine and biology · 2024Review
- Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.EMBO reports · 2023Article
- Editorial: Hypoxia, oxidative stress, and endocrine cancers.Frontiers in endocrinology · 2023Article
- Uncovering the gene regulatory network of type 2 diabetes through multi-omic data integration.Journal of translational medicine · 2022Article
- Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells.Biomolecules · 2022Review
- HIF-2α Preserves Mitochondrial Activity and Glucose Sensing in Compensating β-Cells in Obesity.Diabetes · 2022Article
- β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130.Nature metabolism · 2022Article
- Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice.Bone research · 2022Article
- Retinal hemangioblastoma in a patient with Von Hippel-Lindau disease: A case report and literature review.Frontiers in oncology · 2022Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Defective insulin secretion in response to glucose is an important component of the beta cell dysfunction seen in type 2 diabetes. As mitochondrial oxidative phosphorylation plays a key role in glucose-stimulated insulin secretion (GSIS), oxygen-sensing pathways may modulate insulin release. The von Hippel-Lindau (VHL) protein controls the degradation of hypoxia-inducible factor (HIF) to coordinate cellular and organismal responses to altered oxygenation. To determine the role of this pathway in controlling glucose-stimulated insulin release from pancreatic beta cells, we generated mice lacking Vhl in pancreatic beta cells (betaVhlKO mice) and mice lacking Vhl in the pancreas (PVhlKO mice). Both mouse strains developed glucose intolerance with impaired insulin secretion. Furthermore, deletion of Vhl in beta cells or the pancreas altered expression of genes involved in beta cell function, including those involved in glucose transport and glycolysis, and isolated betaVhlKO and PVhlKO islets displayed impaired glucose uptake and defective glucose metabolism. The abnormal glucose homeostasis was dependent on upregulation of Hif-1alpha expression, and deletion of Hif1a in Vhl-deficient beta cells restored GSIS. Consistent with this, expression of activated Hif-1alpha in a mouse beta cell line impaired GSIS. These data suggest that VHL/HIF oxygen-sensing mechanisms play a critical role in glucose homeostasis and that activation of this pathway in response to decreased islet oxygenation may contribute to beta cell dysfunction.
Indexed as
Identifiers
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.