ArticleCirculation2019
Hyperglycemia-Driven Inhibition of AMP-Activated Protein Kinase α2 Induces Diabetic Cardiomyopathy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes In Vivo.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 2 of them syntheses 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.
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Who cites it
179 citing papers in PubMed, 2 syntheses or guidelines pooled it, 280 citations in OpenAlex.
- Relationship between stress hyperglycaemic ratio (SHR) and critical illness: a systematic review.Cardiovascular diabetology · 2025Pooled it
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- DISC1 Orchestrates Mitochondrial Calcium Overload in Diabetic Encephalopathy Through a Dual Nucleocytoplasmic Mechanism.Biomolecules · 2026Article
- Prospective associations of premature senescence, inflammation, and MERCSs in the cardioprotective effect of CBD in HFpEF.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Mitochondria as the Hub of Apoptosis: A Comprehensive Insight From Mitochondria to Interactions With Other Organelles.MedComm · 2026Review
- Exercise-Induced Regulation of Bone Remodeling via Mitophagy: A Review of Current Evidence.Biomolecules · 2026Review
- Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Research Progress on Downstream Mechanisms of Glucose Metabolic Reprogramming and Its Role in the Occurrence and Progression of Type 2 Diabetes Mellitus.Biomedicines · 2026Review
- Mitochondrial protein OPA3 sustains cardiac function by regulating calcium handling in male mice.Nature communications · 2026Article
- A prognostic model for breast cancer based on mitochondria-associated endoplasmic reticulum membrane (MAM) signature genes.Discover oncology · 2026Article
- Huoxue Qianyang Qutan Recipe limits cardiac remodeling by regulating FUNDC1/IP3R2 signaling pathway in obese hypertensive rats.Scientific reports · 2026Article
- Hyperglycemia impairs cognitive function by inducing mitochondrial damage through lactylation of LRPPRC at K223.EMBO molecular medicine · 2026Article
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- Beyond the Powerhouse: Mitochondrial Crosstalk as a Master Regulator of Cardiac Metabolic Homeostasis and Failure.Journal of cardiovascular translational research · 2026Review
- Emerging Role of Ferroptosis in Diabetes and Associated Complications: When Metabolic Dysregulation Meets Cell Death.Cell proliferation · 2026Review
- The role of mitochondria-associated membranes in tumorigenesis.Discover oncology · 2026Review
- SLC31A1 exon 1 methylation reduces intracellular copper ion and promotes diabetic cardiac fibrosis.Cardiovascular diabetology · 2026Article
- Natural products as multi‑target therapies for sepsis‑induced myocardial dysfunction (Review).International journal of molecular medicine · 2026Review
- TRPV1 in Cardiovascular Disease: A Molecular Nexus of Treatment.Biomolecules · 2026Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
119 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
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundFundc1 (FUN14 domain containing 1), an outer mitochondrial membrane protein, is important for mitophagy and mitochondria-associated endoplasmic reticulum membranes (MAMs). The roles of Fundc1 and MAMs in diabetic hearts remain unknown. The aims of this study, therefore, were to determine whether the diabetes mellitus-induced Fundc1 expression could increase MAM formation, and whether disruption of MAM formation improves diabetic cardiac function.
methodsLevels of FUNDC1 were examined in the hearts from diabetic patients and nondiabetic donors. Levels of Fundc1-induced MAMs and mitochondrial and heart function were examined in mouse neonatal cardiomyocytes exposed to high glucose (HG, 30 mmol/L d-glucose for 48 hours), and in streptozotocin-treated cardiac-specific Fundc1 knockout mice and cardiac-specific Fundc1 knockout diabetic Akita mice, as well.
resultsFUNDC1 levels were significantly elevated in cardiac tissues from diabetic patients in comparison with those from nondiabetic donors. In cultured mouse neonatal cardiomyocytes, HG conditions increased levels of Fundc1, the inositol 1,4,5-trisphosphate type 2 receptor (Ip
conclusionsWe conclude that diabetes mellitus suppresses AMP-activated protein kinase, initiating Fundc1-mediated MAM formation, mitochondrial dysfunction, and cardiomyopathy, suggesting that AMP-activated protein kinase-induced Fundc1 suppression is a valid target to treat diabetic cardiomyopathy.
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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.