ArticleDiabetes2022
HIF-2α Preserves Mitochondrial Activity and Glucose Sensing in Compensating β-Cells in Obesity.
Article in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Molecular Pathways Linking High-Fat Diet and PMBiomolecules · 2024Pooled it
- HIF2A as a prognostic and clinical therapeutic target in ovarian clear cell carcinoma.International journal of cancer · 2026Article
- EPAS1 is associated with human muscle fiber composition and endurance phenotypes.Physiological reports · 2026Article
- Immunometabolism in obesity: Understanding the beneficial and detrimental roles of inflammation.PLoS biology · 2026Article
- Review
- Interactions between lipid droplets and mitochondria in metabolic diseases.Lipids in health and disease · 2025Review
- CCL26 and CXCL12 preserve insulin-sensitizing macrophages in subcutaneous adipose tissue in obesity.Cell reports · 2025Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- Structural Characterization and Antioxidant Activity of Exopolysaccharide Produced from Beet Waste Residue byAntioxidants (Basel, Switzerland) · 2024Article
- HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.Science translational medicine · 2024Article
- Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
In obesity, increased mitochondrial metabolism with the accumulation of oxidative stress leads to mitochondrial damage and β-cell dysfunction. In particular, β-cells express antioxidant enzymes at relatively low levels and are highly vulnerable to oxidative stress. Early in the development of obesity, β-cells exhibit increased glucose-stimulated insulin secretion in order to compensate for insulin resistance. This increase in β-cell function under the condition of enhanced metabolic stress suggests that β-cells possess a defense mechanism against increased oxidative damage, which may become insufficient or decline at the onset of type 2 diabetes. Here, we show that metabolic stress induces β-cell hypoxia inducible factor 2α (HIF-2α), which stimulates antioxidant gene expression (e.g., Sod2 and Cat) and protects against mitochondrial reactive oxygen species (ROS) and subsequent mitochondrial damage. Knockdown of HIF-2α in Min6 cells exaggerated chronic high glucose-induced mitochondrial damage and β-cell dysfunction by increasing mitochondrial ROS levels. Moreover, inducible β-cell HIF-2α knockout mice developed more severe β-cell dysfunction and glucose intolerance on a high-fat diet, along with increased ROS levels and decreased islet mitochondrial mass. Our results provide a previously unknown mechanism through which β-cells defend against increased metabolic stress to promote β-cell compensation in obesity.
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Identifiers
What Socratic 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 Socratic graph.