ArticleAmerican journal of physiology. Endocrinology and metabolism2009
Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein.
Article in American journal of physiology. Endocrinology and metabolism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 114 citations in OpenAlex.
- A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2022Trial
- Verapamil and beta cell function in adults with recent-onset type 1 diabetes.Nature medicine · 2018Trial
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- Role of Divalent Cations in Infections in Host-Pathogen Interaction.International journal of molecular sciences · 2024Review
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- Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies.Cell & bioscience · 2024Review
- Shifting the paradigm of type 1 diabetes: a narrative review of disease modifying therapies.Frontiers in endocrinology · 2024Review
- Verapamil chronicles: advances from cardiovascular to pancreatic β-cell protection.Frontiers in pharmacology · 2023Review
- High-resolution analysis of the cytosolic CaAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients.Medicine and pharmacy reports · 2022Review
- Thioredoxin-Interacting Protein in Cancer and Diabetes.Antioxidants & redox signaling · 2022Review
- AGE-TXNIP axis drives inflammation in Alzheimer's by targeting Aβ to mitochondria in microglia.Cell death & disease · 2022Article
- New Aspects of Diabetes Research and Therapeutic Development.Pharmacological reviews · 2021Review
- Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook.International journal of molecular sciences · 2021Review
- Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation.Lipids in health and disease · 2021Article
- Evaluating the antidiabetic effects of R-verapamil in type 1 and type 2 diabetes mellitus mouse models.PloS one · 2021Article
- Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Gap junctions amplify TRPV4 activation-initiated cell injury via modification of intracellular CaChannels (Austin, Tex.) · 2020Article
- TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis.Antioxidants (Basel, Switzerland) · 2020Review
4 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiomyocyte apoptosis is a critical process in the pathogenesis of ischemic and diabetic cardiomyopathy, but the mechanisms are not fully understood. Thioredoxin-interacting protein (TXNIP) has recently been shown to have deleterious effects in the cardiovascular system and we therefore investigated whether it may also play a role in diabetes-associated cardiomyocyte apoptosis. In fact, TXNIP expression was increased in H9C2 cardiomyocytes incubated at high glucose, and cardiac expression of TXNIP and cleaved caspase-3 were also elevated in vivo in streptozotocin- and obesity-induced diabetic mice. Together, these findings not only suggest that TXNIP is involved in diabetic cardiomyopathy but also that it may represent a novel therapeutic target. Surprisingly, testing putative TXNIP modulators revealed that calcium channel blockers reduce cardiomyocyte TXNIP transcription and protein levels in a dose-dependent manner. Oral administration of verapamil for 3 wk also reduced cardiac TXNIP expression in mice even in the face of severe diabetes, and these reduced TXNIP levels were associated with decreased apoptosis. To determine whether lack of TXNIP can mimic the verapamil-induced decrease in apoptosis, we used TXNIP-deficient HcB-19 mice, harboring a natural nonsense mutation in the TXNIP gene. Interestingly, we found significantly reduced cleaved caspase-3 levels in HcB-19 hearts, suggesting that TXNIP plays a critical role in cardiac apoptosis and that the verapamil effects were mediated by TXNIP reduction. Thus our results suggest that TXNIP reduction is a powerful target to enhance cardiomyocyte survival and that agents such as calcium channel blockers may be useful in trying to achieve this goal and prevent 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.