title: High glucose alters cardiomyocyte contacts and inhibits myofibrillar formation.
abstract: BACKGROUND
  The frequency of diabetes-related heart failure along with the prevalence of diabetes is increasing. Diabetic cardiomyopathy is considered to be a distinct disease in the absence of discernible coronary artery and other defined heart disease. Previously we have shown that glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in cultivated cardiomyocytes.
  
  
  OBJECTIVE
  Here we studied the mechanisms of diabetic cardiomyopathy in more detail.
  
  
  RESULTS
  Streptozotocin-induced diabetes led to a significant increase in cardiac cell apoptosis. Furthermore, cardiomyocyte contacts were reduced. In vitro, prolonged exposure of cultured adult cardiomyocytes to high glucose concentrations drastically reduced myofibrillar formation. In particular, sarcomeric myosin heavy chains and cardiac alpha-actin were reduced, whereas the nonsarcomeric smooth muscle alpha-actin remained unaffected. The deleterious effects of glucose on myofibril formation were prevented by antioxidative regimens.
  
  
  CONCLUSIONS
  Thus, a diabetic milieu leads to multiple structural alterations of the heart including apoptosis, loss of intercellular contacts, and malformation of contractile structures.
authors.affiliation: Division of Endocrinology and Diabetes, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dyntar
authors.forename: Pavel
authors.initials: P
authors.lastname: Sergeev
authors.forename: Jelena
authors.initials: J
authors.lastname: Klisic
authors.forename: Patrice
authors.initials: P
authors.lastname: Ambühl
authors.forename: Marcus C
authors.initials: MC
authors.lastname: Schaub
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007150:Immunohistochemistry; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
chemical_list: D000975:Antioxidants; D003847:Deoxyglucose; D005947:Glucose