Abstract 12755: Metabolic Adaptation of the Heart in a Mouse Model of Type 2 Diabetes Mellitus: A PET Imaging Study
Introduction: Perturbations in myocardial substrate use play a role in a variety of abnormal cardiac states other than ischemic heart disease.
Hypothesis: With diabetes mellitus, there is an overdependence of the heart on fatty-acid utilization with a parallel decline in glucose metabolism. The metabolic response of the heart in diabetes mellitus has thus far not been shown in-vivo in mice.
Methods: We used a mouse model of Type 2 Diabetes Mellitus (T2DM) to evaluate myocardial glucose metabolism in congenic KKAy diabetic mice and KKAA controls, in-vivo. Seven mice 12 weeks of age were evaluated: KKAA non-diabetic controls (n=3) and KKAy diabetic mice (n=4). Dynamic cardiac gated imaging using 18F-FDG was performed with the microPET Focus 120 scanner from Siemens. List mode data acquired from the 60 minute scan was used to construct histograms in 23 time bins over 3 cardiac phases and reconstructed using an iterative OSEM-MAP algorithm with attenuation correction. Regions of interest were drawn in the region corresponding to the left ventricular blood-pool and the myocardium at the end-diastolic (ED) phase of the cardiac cycle. The image derived blood input function and the myocardium time activity curves with partial volume corrections were incorporated into a 3-compartment tracer kinetic model to evaluate the net myocardial glucose influx constant, Ki (1/min).
Results: Figure 1A shows transverse PET slices at the ED phase of the cardiac cycle. The figure demonstrates reduced FDG uptake and increased left ventricular chamber size in the diabetic mice. Figure 1B indicates myocardial time activity curves for FDG in KKAA control and KKAy diabetic mice. The results indicate that the effect of T2DM slows down FDG disposal into the myocardium. Ki is lower in KKAy diabetic mice than in KKAA control mice (figure 1C) by a factor of 2.23 (*p<0.05).
Conclusions: In a model of insulin resistance mice there is a decline in myocardial glucose utilization suggesting metabolic adaptation.
- © 2010 by American Heart Association, Inc.