ArticleJournal of molecular and cellular cardiology2013
Insulin suppresses ischemic preconditioning-mediated cardioprotection through Akt-dependent mechanisms.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Metabolic dependency of malonate protection against cardiac ischemia-reperfusion injury.Basic research in cardiology · 2026Article
- Integration of triglyceride-glucose index and biological aging to predict cardiovascular disease risk in cardiovascular-kidney-metabolic syndrome stages 0-3: a multiple prospective cohort study.Cardiovascular diabetology · 2026Article
- Effect of Small Dense Low-Density Lipoprotein Cholesterol Combined With High-Sensitivity C-Reactive Protein on Cardiometabolic Multimorbidity: A National Cohort Study.Clinical cardiology · 2026Observational
- Predictive value of baseline, cumulative exposure and annual mean changes in TyG-related indices for cardiovascular events in older rural adults with cardiovascular-kidney-metabolic syndrome stages 0-3: a cohort study.Frontiers in endocrinology · 2026Article
- Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3: a prospective cohort study of 282,920 participants in the UK Biobank.Cardiovascular diabetology · 2025Article
- Association of different insulin resistance surrogates with all-cause and cardiovascular mortality among the population with cardiometabolic multimorbidity.Cardiovascular diabetology · 2025Article
- Insulin-Heart Axis: Bridging Physiology to Insulin Resistance.International journal of molecular sciences · 2024Review
- Insulin and glycolysis dependency of cardioprotection by nicotinamide riboside.Basic research in cardiology · 2024Article
- Phenotype of higher post-load insulin response as a predictor of all-cause mortality and cardiovascular mortality in the Chinese non-diabetic population.Diabetology & metabolic syndrome · 2022Article
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- mTOR Mediated Metabolic Rewiring and Ischemic Preconditioning, its Complicated.Circulation research · 2021Article
- Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy.Biochemistry and biophysics reports · 2018Article
- The role of succinate and ROS in reperfusion injury - A critical appraisal.Journal of molecular and cellular cardiology · 2017Review
- Article
- Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy: the case for repeat application as a novel therapy for lower extremity ulceration.Cardiovascular diabetology · 2016Review
- Insulin Signaling and Heart Failure.Circulation research · 2016Review
- Acute hyperglycemia abolishes cardioprotection by remote ischemic perconditioning.Cardiovascular diabetology · 2015Article
- Myocardial autophagic energy stress responses--macroautophagy, mitophagy, and glycophagy.American journal of physiology. Heart and circulatory physiology · 2015Review
- The role of hexokinase in cardioprotection - mechanism and potential for translation.British journal of pharmacology · 2015Review
- Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes.Diabetes · 2015Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
It is believed that the diabetic myocardium is refractory to cardioprotection by ischemic preconditioning (IPC) mainly because of impaired insulin signaling to phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB or Akt). However, human as well as animal studies have clearly showed that the hearts of type 2 diabetic humans and animals may exhibit increased signaling through PI3K-Akt but yet are resistant to cardioprotection by IPC or ischemic post-conditioning. Therefore, this study was designed to determine whether activation of insulin signaling prior to IPC is detrimental for cardioprotection and to assess the role of insulin receptors (IRs) and Akt in mediating this effect. Wild-type (WT) hearts, hearts lacking IRs or hearts expressing an active form of Akt (myrAkt1) were perfused ex vivo using a Langendorff preparation and were subjected to IPC (3cycles of 5min ischemia followed by 5min reflow before 30min no flow ischemia and then by 45min reperfusion) in the presence or absence of 1nmol/L insulin. Interestingly, whereas insulin was protective against I/R (30min no flow ischemia and 45min reperfusion), it completely abolished cardioprotection by IPC in WT hearts but not in mice lacking insulin receptors (IRs) in cardiomyocytes (CIRKO) or in all cardiac cells (TIRKO). The suppression of IPC-mediated cardioprotection was mediated through downstream signaling to Akt and Gsk3β. In addition, transgenic induction of Akt in the heart was sufficient to abrogate IPC even when insulin was absent, further confirming the involvement of Akt in insulin's suppression of cardioprotection by IPC. These data provide evidence that excessive insulin signaling to Akt is detrimental for cardioprotection by IPC and could explain the failure of the diabetic myocardium to precondition.
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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.