Cardiovascular Diabetology (Jul 2009)

Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography

  • Lammertsma Adriaan A,
  • Molthoff Carla FM,
  • Lubberink Mark,
  • Duijst Suzanne,
  • Boontje Nicky M,
  • Vlasblom Ronald,
  • Huisman Marc C,
  • van den Brom Charissa E,
  • van der Velden Jolanda,
  • Boer Christa,
  • Ouwens D Margriet,
  • Diamant Michaela

DOI
https://doi.org/10.1186/1475-2840-8-39
Journal volume & issue
Vol. 8, no. 1
p. 39

Abstract

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Abstract Background In vitro data suggest that changes in myocardial substrate metabolism may contribute to impaired myocardial function in diabetic cardiomyopathy (DCM). The purpose of the present study was to study in a rat model of early DCM, in vivo changes in myocardial substrate metabolism and their association with myocardial function. Methods Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats underwent echocardiography followed by [11C]palmitate positron emission tomography (PET) under fasting, and [18F]-2-fluoro-2-deoxy-D-glucose PET under hyperinsulinaemic euglycaemic clamp conditions. Isolated cardiomyocytes were used to determine isometric force development. Results PET data showed a 66% decrease in insulin-mediated myocardial glucose utilisation and a 41% increase in fatty acid (FA) oxidation in ZDF vs. ZL rats (both p glucose transporter-4 mRNA expression (p Conclusion Using PET and echocardiography, we found increases in myocardial FA oxidation with a concomitant decrease of insulin-mediated myocardial glucose utilisation in early DCM. In addition, the latter was associated with impaired myocardial function. These in vivo data expand previous in vitro findings showing that early alterations in myocardial substrate metabolism contribute to myocardial dysfunction.