title: Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury.
abstract: Diabetes, one of the major risk factors of metabolic syndrome culminates in the development of Ischemic Heart Disease (IHD). Refined diets that lack micronutrients, mainly trivalent chromium (Cr(3+)) have been identified as the contributor in the rising incidence of diabetes. We investigated the effect of niacin-bound chromium (NBC) during ischemia/reperfusion (IR) injury in streptozotocin induced diabetic rats. Rats were randomized into: Control (Con); Diabetic (Dia) and Diabetic rats fed with NBC (Dia+NBC). After 30 days of treatment, the isolated hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. NBC treatment demonstrated significant increase in left ventricular functions and significant reduction in infarct size and cardiomyocyte apoptosis in Dia+NBC compared with Dia. Increased Glut-4 translocation to the lipid raft fractions was also observed in Dia+NBC compared to Dia. Reduced Cav-1 and increased Cav-3 expression along with phosphorylation of Akt, eNOS and AMPK might have resulted in increased Glut-4 translocation in Dia+NBC. Our results indicate that the cardioprotective effect of NBC is mediated by increased activation of AMPK, Akt and eNOS resulting in increased translocation of Glut-4 to the caveolar raft fractions thereby alleviating the effects of IR injury in the diabetic myocardium.
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1110, USA.
authors.forename: Suresh Varma
authors.initials: SV
authors.lastname: Penumathsa
authors.forename: Mahesh
authors.initials: M
authors.lastname: Thirunavukkarasu
authors.forename: Samson Mathews
authors.initials: SM
authors.lastname: Samuel
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhan
authors.forename: Gautam
authors.initials: G
authors.lastname: Maulik
authors.forename: Manashi
authors.initials: M
authors.lastname: Bagchi
authors.forename: Debasis
authors.initials: D
authors.lastname: Bagchi
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Maulik
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism; D022461:Caveolins / Q000378:metabolism; D002857:Chromium / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009525:Niacin / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D022461:Caveolins; D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; D002857:Chromium; D009525:Niacin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases