ArticleDiabetes2018
Metallothionein Preserves Akt2 Activity and Cardiac Function via Inhibiting TRB3 in Diabetic Hearts.
Article in Diabetes, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Effects of Diet Strategy and Nutrients on the Progression and Prevention of Diabetic Cardiomyopathy: A Narrative Review.Food science & nutrition · 2026Review
- Fibroblast growth factor 16: Molecular mechanisms, signalling crosstalk, and emerging roles in cardiac biology and metabolic regulation.Pharmacological research · 2025Review
- Aberrant activation of p53-TRIB3 axis contributes to diabetic myocardial insulin resistance and sulforaphane protection.Journal of advanced research · 2025Article
- Molecular Insights into Oxidative-Stress-Mediated Cardiomyopathy and Potential Therapeutic Strategies.Biomolecules · 2025Review
- Diabetes-associated sleep fragmentation impairs liver and heart functionActa pharmaceutica Sinica. B · 2025Article
- Effects of Dapagliflozin on Myocardial Gene Expression in BTBR Mice with Type 2 Diabetes.Cardiovascular drugs and therapy · 2025Article
- Insulin-Heart Axis: Bridging Physiology to Insulin Resistance.International journal of molecular sciences · 2024Review
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Diabetic cardiomyopathy - Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways.Toxicology and applied pharmacology · 2023Review
- Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies.Biomedicines · 2023Review
- Unveiling the Vital Role of Long Non-Coding RNAs in Cardiac Oxidative Stress, Cell Death, and Fibrosis in Diabetic Cardiomyopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Cardiac metallothionein overexpression rescues diabetic cardiomyopathy in Akt2-knockout mice.Journal of cellular and molecular medicine · 2021Article
- The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.Cardiovascular diabetology · 2021Observational
- Application of Animal Models in Diabetic Cardiomyopathy.Diabetes & metabolism journal · 2021Review
- Traditional Chinese Medication Qiliqiangxin Attenuates Diabetic Cardiomyopathy via Activating PPARγ.Frontiers in cardiovascular medicine · 2021Article
- Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence.Nature reviews. Cardiology · 2020Review
- Article
- Abnormal DNA methylation patterns in patients with infection‑caused leukocytopenia based on methylation microarrays.Molecular medicine reports · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Cardiac insulin resistance is a key pathogenic factor for diabetic cardiomyopathy (DCM), but the mechanism remains largely unclear. We found that diabetic hearts exhibited decreased phosphorylation of total Akt and isoform Akt2 but not Akt1 in wild-type (WT) male FVB mice, which was accompanied by attenuation of Akt downstream glucose metabolic signal. All of these signal changes were not observed in metallothionein cardiac-specific transgenic (MT-TG) hearts. Furthermore, insulin-induced glucose metabolic signals were attenuated only in WT diabetic hearts. In addition, diabetic hearts exhibited increased Akt-negative regulator tribbles pseudokinase 3 (TRB3) expression only in WT mice, suggesting that MT may preserve Akt2 function via inhibiting TRB3. Moreover, MT prevented tert-butyl hydroperoxide (tBHP)-reduced insulin-stimulated Akt2 phosphorylation in MT-TG cardiomyocytes, which was abolished by specific silencing of Akt2. Specific silencing of TRB3 blocked tBHP inhibition of insulin-stimulated Akt2 phosphorylation in WT cardiomyocytes, whereas overexpression of TRB3 in MT-TG cardiomyocytes and hearts abolished MT preservation of insulin-stimulated Akt2 signals and MT prevention of DCM. Most importantly, supplementation of Zn to induce MT preserved cardiac Akt2 signals and prevented DCM. These results suggest that diabetes-inhibited cardiac Akt2 function via TRB3 upregulation leads to aberrant cardiac glucose metabolism. MT preservation of cardiac Akt2 function by inhibition of TRB3 prevents DCM.
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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.