Sarcoplasmic Ca2+ release is prolonged in nonfailing myocardium of diabetic patients

Hannes Reuter, Sabine Grönke, Christian Adam, Maida Ribati, Jan Brabender, Carsten Zobel, Konrad F. Frank, Jens Wippermann, Robert H.G. Schwinger, Klara Brixius, Jochen Müller-Ehmsen

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background: Asymptomatic diabetic patients have a high incidence of clinically unrecognized left ventricular dysfunction with an abnormal cardiac response to exercise. We, therefore, examined subclinical defects in the contraction-relaxation cycle and intracellular Ca2+ regulation in myocardium of asymptomatic type 2 diabetic patients. Methods: Alterations in the dynamics of the intracellular Ca2+ transient and contractility were recorded in right atrial myocardium of type 2 diabetic patients and non-diabetic control tissue loaded with fura-2. In order to gain an insight into mechanisms underlying the altered Ca2+ handling in diabetic myocardium levels of mRNA, protein expression and phosphorylation of key proteins in sarcoplasmic Ca2+ handling were determined. Results: In isolated atrial trabeculae of diabetic myocardium the rise of systolic Ca2+ was significantly prolonged, but relaxation of the Ca2+ transient was unaltered compared to control tissue. Accordingly, the levels of expression of mRNA and protein of the Ca2+ release channel (RyR2) of the sarcoplasmic reticulum were reduced by 68 and 22%, respectively. Endogenous phosphorylation of RyR2 by protein kinases C, however, was increased by 31% in diabetic myocardium, as assessed by the back-phosphorylation technique. Levels of expression of SERCA2 and phospholamban were unaltered between both groups. Conclusions: Intracellular Ca2+ release is prolonged in non-failing myocardium of type 2 diabetic patients and this may be primarily due to a decreased expression of RyR2. This defective Ca2+ release may represent an early stage of ventricular dysfunction in type 2 diabetes and would favor the abnormal response to exercise frequently observed in asymptomatic diabetic patients.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalMolecular and Cellular Biochemistry
Issue number1-2
StatePublished - Jan 2008
Externally publishedYes


  • Back-phosphorylation
  • Human myocardium
  • Protein kinase C
  • Ryanodine receptors
  • Sarcoplasmic Ca release
  • Type 2 diabetes

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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