title: Effect of gamma-carboxylase inhibition on serum osteocalcin may be partially protective against developing diabetic cardiomyopathy in type 2 diabetic rats.
abstract: To investigate the possible protective effect of elevated undercarboxylated osteocalcin on diabetic cardiomyopathy mechanisms and risk factors.
  
  
  
  In all, 32 male rats were divided into four groups: control, diabetic, diabetic warfarin and normal warfarin-treated groups. Isolated heart functions were assessed; fasting serum insulin, glucose and glycosylated haemoglobin, homeostasis model assessment insulin resistance and lipid profile were investigated. Serum undercarboxylated osteocalcin and adiponectin were also measured. In cardiac tissue, malondialdehyde content, acyl-CoA dehydrogenase gene expression, Bax/Bcl2 ratio, sarcoendoplasmic reticulum calcium ATPase and osteocalcin receptor (G protein-coupled receptor family C group 6 member A) genes expression were investigated.
  
  
  
  Prophylactic elevation of undercarboxylated osteocalcin was accompanied by improved insulin sensitivity and lipid profile, increased serum adiponectin, upregulated myocardial osteocalcin receptor with preserved left ventricular function, decreased cardiac malondialdehyde content, acyl-CoA dehydrogenase and Bax/Bcl2 ratio.
  
  
  
  Undercarboxylated osteocalcin was suggested to have protective effects against diabetic cardiomyopathy, possibly through direct action on upregulated G protein-coupled receptor family C group 6 member A and indirectly via adiponectin. These effects may be mediated through antagonizing oxidative stress and apoptosis.
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt sarahmahmoud@cu.edu.eg.
authors.forename: Sarah Mahmoud
authors.initials: SM
authors.lastname: Gamal
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Nermeen Bakr
authors.initials: NB
authors.lastname: Sadek
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Laila Ahmed
authors.initials: LA
authors.lastname: Rashed
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Heba Mohamed
authors.initials: HM
authors.lastname: Shawky
authors.affiliation: Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Maha Mohamed
authors.initials: MM
authors.lastname: Gamal El-Din
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019735:Carbon-Carbon Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D058065:Diabetic Cardiomyopathies / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D015675:Osteocalcin / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D001786:Blood Glucose; D004791:Enzyme Inhibitors; C522394:GPRC6A protein, rat; D007328:Insulin; D008055:Lipids; D043562:Receptors, G-Protein-Coupled; D015675:Osteocalcin; D008315:Malondialdehyde; D014859:Warfarin; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase
keywords: Diabetes mellitus; adiponectin; diabetic cardiomyopathy; undercarboxylated osteocalcin; warfarin