title: Intermittent insulin treatment mimics ischemic postconditioning via MitoKATP channels, ROS, and RISK.
abstract: OBJECTIVE
  It has previously been demonstrated that 15-min continuous insulin infusion at immediate reperfusion affords cardioprotection. This study sought to reduce the treatment time of insulin and test if intermittent insulin infusions can mimic ischemic postconditioning.
  
  
  METHODS
  In a Langendorff perfused rat heart model of regional ischemia, hearts were at the onset of reperfusion subjected to either 5- or 1-min continuous insulin infusion or 3 × 30 s intermittent insulin infusions (InsPost); with or without inhibitors of Akt (SH-6), p70s6-kinase (rapamycin), mitochondrial ATP-sensitive potassium channels (5-hydroxydecanoic acid [5-HD]), or a scavenger of reactive oxygen species (ROS; 2-mercaptopropionyl glycine [MPG]). Infarct size is expressed as percent of area at risk and presented as mean ± standard error of the mean or s.e.m.
  
  
  RESULTS
  Only InsPost was able to reduce infarct size compared with controls (InsPost 33 ± 6% vs. Ctr 52 ± 4%, p < 0.05.). This cardioprotection was abrogated by co-administering SH-6, rapamycin, 5-HD, or MPG. (InsPost + SH-6 56 ± 9%, InsPost + Rapa 55 ± 8%, InsPost + 5-HD 56 ± 7%, InsPost + MPG 60 ± 3% vs. InsPost 33 ± 6% p < 0.05). These results were corroborated by a significant increase in phosphorylated Akt and p70s6k in the InsPost group compared with controls.
  
  
  CONCLUSIONS
  Short intermittent insulin infusions can mimic ischemic postconditioning and reduce myocardial infarct size via Akt/p70s6k and mKATP channels/ROS-dependent signaling.
authors.affiliation: a Department of Biomedicine , Faculty of Medicine and Dentistry, University of Bergen , Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Helgeland
authors.forename: Lars
authors.initials: L
authors.lastname: Breivik
authors.forename: Balindiwe J
authors.initials: BJ
authors.lastname: Sishi
authors.forename: Anna-Mart
authors.initials: AM
authors.lastname: Engelbrecht
authors.forename: Anne K
authors.initials: AK
authors.lastname: Jonassen
mesh_terms: D000818:Animals; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage*; D057775:Ischemic Postconditioning; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa
keywords: RISK; ROS; cardioprotection; insulin; ischemia; postconditioning; reperfusion injury; reperfusion therapy