Time course of alterations in myocardial glucose utilization in the Zucker diabetic fatty rat with correlation to gene expression of glucose transporters: a small-animal PET investigation.
Diabetic cardiomyopathy is associated with abnormalities in glucose metabolism. We evaluated myocardial glucose metabolism in a rodent model of type 2 diabetes, namely the Zucker diabetic fatty (ZDF) rat, and validated PET measurements of glucose uptake against gene and protein expression of glucose transporters (GLUTs).


METHODS
Six lean and ZDF rats underwent small-animal PET at the age of 14 wk and at the age of 19 wk. The imaging protocol consisted of a 60-min dynamic acquisition with 18F-FDG (18.5-29.6 MBq). Dynamic images were reconstructed using filtered backprojection with a 2.5 zoom on the heart and 40 frames per imaging session. PET measurements of myocardial glucose uptake (MGUp) rate and utilization were determined with an input function derived by the hybrid image-blood-sampling algorithm on recovery-corrected anterolateral myocardial regions of interest. After the PET session at week 19 (W19), hearts were extracted for gene and protein expression analysis of GLUT-1 and GLUT-4. The dependence of MGUp on gene expression of GLUT-1 and GLUT-4 was characterized by multiple-regression analysis.


RESULTS
MGUp in ZDF rats at both week 14 (W14) and W19 (P < 0.006) was significantly lower than MGUp in lean littermate control rats. Moreover, lean rats at W19 displayed significantly higher MGUp than they did at W14 (P = 0.007). Consistent with a diminished MGUp result, gene expression of GLUT-4 was significantly (P = 0.004) lower in ZDF rats. Finally, MGUp significantly (P = 0.0003) correlated with gene expression of GLUT-4.


CONCLUSIONS
Using small-animal PET, we confirmed alterations in myocardial glucose utilization and validated PET measurement of MGUp against gene and protein expression of GLUTs in the diabetic heart of an animal model of type 2 diabetes.
Shoghi
Kooresh I
KI
Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. shoghik@wustl.edu
Gropler
Robert J
RJ
Sharp
Terry
T
Herrero
Pilar
P
Fettig
Nicole
N
Su
Yi
Y
Mitra
Mayurranjan S
MS
Kovacs
Attila
A
Finck
Brian N
BN
Welch
Michael J
MJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis*; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D011924:Rats, Zucker
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D019275:Radiopharmaceuticals; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D019788:Fluorodeoxyglucose F18; D005947:Glucose