Insulin induced cytoprotection by mimicking postconditioning at myocardial reperfusion

Helgeland, Erik; Guvåg, Steinar; Jonassen, Anne K.

doi:10.1016/j.yjmcc.2007.03.567

Cited by 5 publications

(10 citation statements)

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“…These include inhalation anaesthetics like isoflurane [127,130,135] and sevoflurane [31] and volatile anaesthetics [136]. Further 2,3,4,5-tetrahydroxylstilbene-2-O-glucoside extracted from dried root tubers of Polygonum multiforum (polygonaceae) [137], insulin [120,138,139], 17-b estradiol [140][141][142][143][144][145][146], genistein [147], urocortin [148], cardiotrophin, levosimendon (inodilator) [133], statins like atorvastatin [149,150], opioids [150], growth factors like insulin growth factor-1 and transforming growth factor-b [58,151], GLP-1 [152], ADO [153] and ADO analogues [154][155][156][157] bradykinin, nitric-oxide [54,55,158] adipocytokines, natriuretic peptides and EPO [136]. These are the examples of PoCo mimetics which have been explored to induce pharmacological PoCo protection.…”

Section: P H a R M A C O L O G I C A L P O S T C O N D I T I O N I N Gmentioning

confidence: 99%

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Molecular aspects of ischaemic postconditioning

Kaur

Jaggi²,

Singh

2009

Fundamemntal Clinical Pharma

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Preconditioning, a well established phenomenon had been used since 1980s to attenuate ischaemia-reperfusion induced injury. However, inability to predict the onset of ischaemia in clinical settings led to the discovery of a new concept of postconditioning (PoCo), in 2000s whereby brief repetitive cycles of ischaemia with intermittent reperfusion followed by prolonged ischaemia-elicited tissue protection. There is an impressive array of molecular mechanisms contributing to PoCo-mediated tissue-protection, which include triggers like adenosine (ADO), opioid, erythropoietin (EPO), endogenous nitric-oxide, reactive oxygen species, acetylcholine, tissue factors, pro-inflammatory cytokines and bradykinin; mediators like reperfusion injury salvage kinase pathways including phosphoinositide-3-kinase, extra-cellular signal regulated kinase(1/2) pathway, protein kinase G and protein kinase C; end-effectors like mitochondrial permeability transition pore and mitochondrial potassium ATP channel. The clinical applicability of PoCo has been extended with the use of PoCo mimetic agents like insulin, glucagon like peptide, EPO, statins and ADO before reperfusion in patients with ischaemia reperfusion injury. Remote PoCo has also emerged as a new concept; however, considerable research is required for understanding its molecular mechanisms. In this review, an exhaustive attempt has been made to unearth some molecular aspects of PoCo.

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Section: P H a R M A C O L O G I C A L P O S T C O N D I T I O N I N Gmentioning

confidence: 99%

“…At molecular level, the protective effect of these pharmacological postconditioning agents appears to be mediated by ERK½, p70S6K and eNOS [130,159], further by Akt/PKB [120], PI3K-Akt [144][145][146][147] and by end effectors like mPTP [127,135] and by mK ATP [31,133,137,141] .…”

Section: P H a R M A C O L O G I C A L P O S T C O N D I T I O N I N Gmentioning

confidence: 99%

Molecular aspects of ischaemic postconditioning

Kaur

Jaggi²,

Singh

2009

Fundamemntal Clinical Pharma

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“…Pharmacological intervention with insulin has in several studies shown that insulin administration at the moment of reperfusion during an acute myocardial infarction (AMI) can activate cell survival programmes and diminish lethal reperfusion injury in the in vitro and the ex vivo rat heart [1–4]. These studies have challenged the negative clinical studies in AMI using intravenous glucose‐insulin‐potassium (GIK) treatment in cardiac protection [5,6], emphasizing on insulin intracellular cell survival signalling via the Akt and p70s6 kinase pathway, as opposed to the predicted cardio‐protective effect of treatment with glucose and potassium or a reduction in the level of free fatty acids.…”

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confidence: 99%

“…Fasting animals. The effective insulin dose to reduce infarct size when given during reperfusion in ex vivo rat hearts (Langendorff model) is known [2–4]. An equivalent dose for pigs was calculated to be 840 mU which was the starting dose in this study, assuming pig heart weight as 0.5% of total body‐weight.…”

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confidence: 99%

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Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Slettom

Jonassen

Tuseth

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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Insulin given at immediate reperfusion reduces myocardial infarct size in the in vitro and the ex vivo rat heart. In vivo, insulin may cause hypoglycaemia, hypokalaemia and elevation of catecholamines, potentially harmful during an acute myocardial infarction. The purpose of this study was to evaluate tolerance and safety of intracoronary insulin infusions in a porcine model applying percutaneous intervention techniques.

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Influence of Feeding and Intracoronary Dose on Insulin‐Mediated Relative Akt Phosphorylation in the Porcine Myocardium

Slettom

Jonassen

Breivik

et al. 2013

Cardiovascular Therapeutics

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SUMMARYAims: Insulin promotes Akt-dependent prosurvival signaling and reduces experimental ischemia reperfusion injury, but its clinical impact has been limited. Further understanding of the interplay between insulin and Akt in the myocardium of relevant large animal models is needed. We aimed to investigate (1) Akt phosphorylation, (2) influence of feeding state, and (3) impact of dose on the Akt response following intracoronary insulin administration in the nonischemic porcine heart. Methods: Pigs fed 2 h preprocedure received 0.1 U (unit) or 1.0 U of insulin in the left coronary artery and fasting pigs 0.1 U. Left and right ventricle tissues harvested 15 min postinsulin administration were analyzed for Akt phosphorylation by densitometric analyses of total Akt and phosphorylated Akt immunoblots expressed as a ratio and normalized against left auricle biopsies at baseline. Results: Median relative Akt phosphorylation across all biopsy locations increased significantly from baseline in both fasting and fed animals after insulin infusion: 371.4% (P < 0.001) in the fasting-0.1 U insulin group, 202.7% (P = 0.003) in the fed-1.0 U group and 131.5% (P < 0.001) in the fed-0.1 U group. The increase was significantly higher for the fasting-0.1 U and the fed-1.0 U groups as compared with the fed-0.1 U group. Baseline serum glucose in fed and fasting pigs was 6.3 AE 0.3 versus 5.2 AE 0.4 mM (P = 0.050), respectively. Conclusions: Preexperimental feeding attenuates the median relative rise in Akt phosphorylation mediated by exogenous insulin in the porcine heart, and higher insulin doses are therefore required in fed compared with fasting animals.

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Insulin induced cytoprotection by mimicking postconditioning at myocardial reperfusion

Cited by 5 publications

References 0 publications

Molecular aspects of ischaemic postconditioning

Molecular aspects of ischaemic postconditioning

Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Influence of Feeding and Intracoronary Dose on Insulin‐Mediated Relative Akt Phosphorylation in the Porcine Myocardium

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