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J Nucl Med. 2008; 49 (Supplement 1):32P
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Cardiovascular: Basic Science

Small Animal Imaging

Assessing the efficacy of anti-diabetic therapies on myocardial glucose utilization in an animal model of type 2 diabetes (T2D) with PET

Kooresh Shoghi1, Robert Gropler1, Brian Finck1, Terry Sharp1, Pillar Herrero1, Nicole Fettig1 and Michael Welch1

1 Department of Radiology, Washington University in St. Louis, St. Louis, Missouri


Formula

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Objectives: Diabetic cardiomyopathy is associated with abnormalities in myocardial fuel metabolism. We evaluate myocardial glucose uptake rate (MGUp) in a rodent model of T2D and assess the mechanism by which drug therapies affect MGUp using gene expression (GeEx) analysis.

Methods: The study utilized 18 Zucker Diabetic Fatty (ZDF) rats and 6 littermate controls divided evenly into 4 groups: Lean, ZDF, Metformin (MET)-treated ZDF, and Rosiglitazone (ROSI)-treated ZDF all fasted overnight. Rats underwent 60min small animal PET imaging with FDG at age 14 weeks (W14) and 19 weeks (W19). Treatment was provided in the diet following W14 and lasted for 4 weeks. PET Images were reconstructed using Filtered Back Projection. MGUp was determined with input function derived by the HIBS algorithm on recovery-corrected myocardial regions of interest. Following W19, hearts were extracted for GeEx analysis of GLUT1 and GLUT4.

Results: Lean rats had significantly higher MGUp than age-matched ZDF rats at both W14 and W19 (P<0.02). Treatment with either MET or ROSI significantly (P=0.05 and P=0.005, respectively) enhanced MGUp with ROSI being significantly more effective (P=0.04). The Spearman correlation between MGUp and GeEx of GLUT1 and GLUT4 was r=0.69 and r=0.73, respectively. In particular, ROSI significantly (P=0.004) enhanced GeEx of GLUT4 while GeEx of GLUT1 was only marginally not significant (P=0.07).

Conclusions: MGUp correlated with GeEx pattern of GLUT under various physiological conditions and therapeutic challenges. ROSI enhanced MGUp by up-regulation of GLUT4 and marginally GLUT1. These findings underscore both the translational capability and the potential use of small animal PET in drug development.

Research Support: NIH/NHLBI 5PO1HL13851





This Article
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Shoghi, K.
Right arrow Articles by Welch, M.
PubMed
Right arrow Articles by Shoghi, K.
Right arrow Articles by Welch, M.