ArticleDiabetes2021
Activation of HIF1α Rescues the Hypoxic Response and Reverses Metabolic Dysfunction in the Diabetic Heart.
Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators.Frontiers in cellular neuroscience · 2023Pooled it
- Amyloid-Forming Amylin Secreted by the Pancreas Promotes Hypoxia-Inducible Factor Activation and Mitochondrial Alterations in Liver and Heart During Type 2 Diabetes Pathogenesis.Comprehensive physiology · 2026Article
- Impaired Glycolysis Leads to Defective Efferocytosis and Impaired Plaque Resolution inCirculation · 2026Article
- Diet-Associated Regulation of Cardiac Metabolism: Molecular Determinants and Pathophysiological Consequences.Nutrients · 2026Review
- Early Perioperative Changes in Circulating Hypoxia-Inducible Factor-1 Alpha (HIF-1A) and Vascular Endothelial Growth Factor (VEGF) Following Lower Limb Revascularisation for Peripheral Arterial Disease.Journal of clinical medicine · 2026Article
- Modulation of the gut-heart axis by exercise in diabetic cardiomyopathy: Microbial mechanisms and clinical implications.iScience · 2026Review
- Distinct immunometabolic signatures of type 1 versus type 2 diabetes in a murine model of myocardial infarction.Cardiovascular diabetology · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Metabolic syndrome reduces but does not eliminate the cardioprotective effect of adaptation to hypoxia: the link with changes in the opioid system.Pflugers Archiv : European journal of physiology · 2025Article
- Article
- FoxO1-zDHHC4-CD36 S-Acylation Axis Drives Metabolic Dysfunction in Diabetes.Circulation research · 2025Article
- Cardiomyocytes in Hypoxia: Cellular Responses and Implications for Cell-Based Cardiac Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
- Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.Cardiovascular drugs and therapy · 2025Article
- Thermosensitive Hydrogel with Programmable, Self-Regulated HIF-1α Stabilizer Release for Myocardial Infarction Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The multifaceted role of mitochondria in cardiac function: insights and approaches.Cell communication and signaling : CCS · 2024Review
- Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection.International journal of drug discovery and pharmacology · 2024Article
- Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress.Cellular and molecular life sciences : CMLS · 2024Article
- Redefining Diabetic Cardiomyopathy: Perturbations in Substrate Metabolism at the Heart of Its Pathology.Diabetes · 2024Review
- Transcriptional Responses of Different Brain Cell Types to Oxygen Decline.Brain sciences · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes (T2D) impairs hypoxia-inducible factor (HIF)1α activation, a master transcription factor that drives cellular adaptation to hypoxia. Reduced activation of HIF1α contributes to the impaired post-ischemic remodeling observed following myocardial infarction in T2D. Molidustat is an HIF stabilizer currently undergoing clinical trials for the treatment of renal anemia associated with chronic kidney disease; however, it may provide a route to pharmacologically activate HIF1α in the T2D heart. In human cardiomyocytes, molidustat stabilized HIF1α and downstream HIF target genes, promoting anaerobic glucose metabolism. In hypoxia, insulin resistance blunted HIF1α activation and downstream signaling, but this was reversed by molidustat. In T2D rats, oral treatment with molidustat rescued the cardiac metabolic dysfunction caused by T2D, promoting glucose metabolism and mitochondrial function, while suppressing fatty acid oxidation and lipid accumulation. This resulted in beneficial effects on post-ischemic cardiac function, with the impaired contractile recovery in T2D heart reversed by molidustat treatment. In conclusion, pharmacological HIF1α stabilization can overcome the blunted hypoxic response induced by insulin resistance. In vivo this corrected the abnormal metabolic phenotype and impaired post-ischemic recovery of the diabetic heart. Therefore, molidustat may be an effective compound to further explore the clinical translatability of HIF1α activation in the diabetic heart.
Indexed as
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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.