Pretreatment with insulin before ischaemia reduces infarct size in Langendorff-perfused rat hearts
Autor: | Ole D. Mjøs, Anne K. Jonassen, Britt N. Fuglesteg, Crina Tiron, Kirsti Ytrehus |
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Rok vydání: | 2009 |
Předmět: |
Male
medicine.medical_specialty Physiology medicine.medical_treatment Myocardial Infarction chemistry.chemical_compound Internal medicine medicine Animals Hypoglycemic Agents Insulin cardiovascular diseases Rats Wistar Protein kinase B PI3K/AKT/mTOR pathway Evans Blue Cardioprotection Sirolimus biology business.industry TOR Serine-Threonine Kinases medicine.disease Rats Oncogene Protein v-akt Perfusion Insulin receptor Endocrinology chemistry Ischemic Preconditioning Myocardial Models Animal biology.protein Phosphorylation business Reperfusion injury Protein Kinases |
Zdroj: | Acta physiologica (Oxford, England). 195(2) |
ISSN: | 1748-1716 |
Popis: | Aim: To compare the possible role of Akt and mammalian target of rapamycin (mTOR) in mediating cardioprotection against ischaemia under three different conditions: (1) During ischaemic preconditioning (IPC), (2) when insulin was given as a pretreatment agent (InsPC) and (3) when insulin was given as a reperfusion cell survival agent (InsR). Methods: Isolated perfused rat hearts were subjected to IPC (3 × 5 min) or InsPC (50 mU mL−1; 3 × 5 min), before 30 min of regional ischaemia followed by 120 min of reperfusion ± 1L-6-hydroxymethyl-chiro-inositol-2-[(R)-2-O-methyl-3-O-octadecylcarbonate] (HIMO) (20 μm; Akt inhibitor) or rapamycin (1 nm; mTOR inhibitor). In addition, insulin (3 mU mL−1) was given at the onset of reperfusion, ±HIMO or rapamycin. Risk zone (R) and infarct size (I) were determined with Evans blue and tetrazolium staining respectively. Western blot analysis was performed on tissue from Langendorff-perfused rat hearts and cell lysates from cultured HL1 cells. Results: IPC, InsPC and InsR treatment resulted in a significant reduction in infarct size compared to controls (all P |
Databáze: | OpenAIRE |
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