Insulin/NFκB protects against ischemia-induced necrotic cardiomyocyte death

Diaz, Ariel; Humeres, Claudio; González, Verónica; Gómez, Marı́a; Montt, Natalia; Pecchi, Gina; Chiong, Mario; Garcı́a, Lorena

doi:10.1016/j.bbrc.2015.09.171

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…For the mechanisms involved, the PI3K/AKT pathway is speculated to be the contributor upregulating the HSP70 in insulin preconditioning (Ji, Xue, Cheng, & Bai, ), because it is activated by insulin pretreatment in I/R hearts (Venardos et al, ; H. Yao, Han, & Han, ) and contributes to HSP70 overexpression in several other preconditioning (Ji et al, ; Q. Li et al, ). Additionally, the result of another experiment, which was performed in rat I/R hearts pretreated with insulin, suggested that insulin preconditioning reduced necrosis of cardiomyocytes through a NF‐κB‐related mechanism (Diaz et al, ). As NF‐κB has been shown to be a stimulator for HSP70 overexpression in IPC, whether the NF‐κB/HSP70 pathway is also activated and contributes to cardioprotection may be an interesting direction for elucidating the mechanisms of insulin‐induced cardioprotective effects.…”

Section: Hsp70: Involvement In Conditioning Against Myocardial I/r In...mentioning

confidence: 99%

Heat shock protein 70: A promising therapeutic target for myocardial ischemia–reperfusion injury

Song

Zhong

Wang

2018

Journal Cellular Physiology

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Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, which may instead induce cardiomyocyte necrosis due to myocardial ischemia-reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress-inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis-related proteins) and signaling pathways (e.g., c-Jun N-terminal kinase pathway and extracellular-signal-regulated kinase 1/2 pathway), forming a complicated network that contributes to reducing reactive oxygen species accumulation, improving calcium homeostasis, inhibiting cellular apoptosis, thereby enhancing the stress adaption of myocardium to I/R injury. In addition, the extracellular HSP70, which is released from injured cardiomyocytes during I/R, acts as a proinflammatory mediator that results in cell death, while the intracellular HSP70 exerts antiinflammatory effects by suppressing proinflammatory signaling pathways. Notably, HSP70 is induced and contributes to the cardioprotection in several types of preconditioning and postconditioning. Meanwhile, it is shown that the cardioprotective effectiveness of preconditioning-induced HSP70 (e.g., hyperthermia preconditioning-induced HSP70) can be impaired by certain pathological conditions, such as hyperlipidemia and hyperglycemia. Thus, we highlight the widespread cardioprotective involvement of HSP70 in preconditioning and postconditioning and elucidate how HSP70-mediated cardioprotection is impaired in these pathological conditions. Furthermore, several therapeutic potentials of HSP70 against myocardial I/R injury and potential directions for future studies are also provided in this review.

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Section: Hsp70: Involvement In Conditioning Against Myocardial I/r In...mentioning

confidence: 99%

Heat shock protein 70: A promising therapeutic target for myocardial ischemia–reperfusion injury

Song

Zhong

Wang

2018

Journal Cellular Physiology

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“…Although a comprehensive understanding of the mechanisms underlying insulin action in the heart is only just emerging, there is abundant evidence that insulin impacts cardiac metabolism by influencing a wide range of cellular processes, such as glucose transport, glycolysis, glycogen synthesis (Abel, 2004 ), cardiac hypertrophy, protein synthesis, lipid metabolism (Belke et al, 2002 ). Moreover, insulin also participates in myocardial contractility (Fu et al, 2014 ), protection against ischemia-induced necrotic death (Diaz et al, 2015 ), autophagy (Riehle et al, 2013 ), and cell survival, either directly or through the closely associated insulin-like growth factor-1 (IGF-1) (Troncoso et al, 2014 ).…”

Section: Insulin Signaling In the Normal Heartmentioning

confidence: 99%

New Molecular Insights of Insulin in Diabetic Cardiomyopathy

et al. 2016

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Type 2 diabetes mellitus (T2DM) is a highly prevalent disease worldwide. Cardiovascular disorders generated as a consequence of T2DM are a major cause of death related to this disease. Diabetic cardiomyopathy (DCM) is characterized by the morphological, functional and metabolic changes in the heart produced as a complication of T2DM. This cardiac disorder is characterized by constant high blood glucose and lipids levels which eventually generate oxidative stress, defective calcium handling, altered mitochondrial function, inflammation and fibrosis. In this context, insulin is of paramount importance for cardiac contractility, growth and metabolism and therefore, an impaired insulin signaling plays a critical role in the DCM development. However, the exact pathophysiological mechanisms leading to DCM are still a matter of study. Despite the numerous questions raised in the study of DCM, there have also been important findings, such as the role of micro-RNAs (miRNAs), which can not only have the potential of being important biomarkers, but also therapeutic targets. Furthermore, exosomes also arise as an interesting variable to consider, since they represent an important inter-cellular communication mechanism and therefore, they may explain many aspects of the pathophysiology of DCM and their study may lead to the development of therapeutic agents capable of improving insulin signaling. In addition, adenosine and adenosine receptors (ARs) may also play an important role in DCM. Moreover, the possible cross-talk between insulin and ARs may provide new strategies to reverse its defective signaling in the diabetic heart. This review focuses on DCM, the role of insulin in this pathology and the discussion of new molecular insights which may help to understand its underlying mechanisms and generate possible new therapeutic strategies.

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“…Several animal studies have shown the protective effects of insulin on the heart [137]. A recent study shows that insulin decreased necrosis in cardiomyocytes during ischemia through an Akt/NFκB pathway [138]. The beneficial effect of insulin in the post-ischemic functional improvement in responding to βAR agonist is likely due to the increased cell survival and subsequent more functional cardiomyocytes available within the I/R hearts [25].…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors

Shi²,

West

et al. 2017

Journal of Cardiovascular Pharmacology

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Summary Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between two receptor signaling systems, and forming an integrated and dynamic network. Moreover, insulin can drive cardiac adrenergic desensitization via PKA and GRK phosphorylation of the β2AR, which compromises adrenergic regulation of cardiac contractile function. In this review, we will explore the current state of knowledge linking insulin and GPCR signaling, especially βAR signaling in the heart, with emphasis on molecular insights regarding its role in diabetic cardiomyopathy (DCM).

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Insulin/NFκB protects against ischemia-induced necrotic cardiomyocyte death

Cited by 9 publications

References 42 publications

Heat shock protein 70: A promising therapeutic target for myocardial ischemia–reperfusion injury

Heat shock protein 70: A promising therapeutic target for myocardial ischemia–reperfusion injury

New Molecular Insights of Insulin in Diabetic Cardiomyopathy

Cross-Talk Between Insulin Signaling and G Protein–Coupled Receptors

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