Assessment of myocardial metabolism in diabetic rats using small-animal PET: a feasibility study.
This feasibility study was undertaken to determine whether kinetic modeling in conjunction with small-animal PET could noninvasively quantify alterations in myocardial perfusion and substrate metabolism in rats.


METHODS
All small-animal PET was performed on either of 2 tomographs. Myocardial blood flow and substrate metabolism were measured in 10 male Zucker diabetic fatty rats (ZDF, fa/fa) and 10 lean littermates (Lean, Fa/+) using (15)O-water, 1-(11)C-glucose, 1-(11)C-acetate, and 1-(11)C-palmitate. Animals were 12.0 +/- 1.4-wk old.


RESULTS
Consistent with a type 2 diabetic phenotype, the ZDF animals showed higher plasma hemoglobin A(1c), insulin, glucose, and free fatty acid (FFA) levels than their lean controls. Myocardial glucose uptake (mL/g/min) was not significantly different between the 2 groups. However, higher glucose plasma levels in the ZDF rats resulted in higher myocardial glucose utilization (nmol/g/min) (Lean, 629 +/- 785, vs. ZDF, 1,737 +/- 1,406; P = 0.06). Similarly, myocardial FFA uptake (mL/g/min) was not significantly different between the 2 groups, (Lean, 0.51 +/- 28, vs. ZDF, 0.72 +/- 0.19; P = not significant) However, due to higher FFA plasma levels, utilization and oxidation (nmol/g/min) were significantly higher in the ZDF group (Lean, 519 +/- 462, vs. ZDF, 1,623 +/- 712, P < .001; and Lean, 453 +/- 478, vs. ZDF, 1,636 +/- 730, P < .01).


CONCLUSIONS
Noninvasive measurements of myocardial substrate metabolism in ZDF rats using small-animal PET are consistent with the expected early metabolic abnormalities that occur in this well-characterized model of type 2 diabetes mellitus. Thus, small-animal PET demonstrates significant promise in providing a means to link the myocardial metabolic abnormalities that occur in rat of disease with the human condition.
Welch
Michael J
MJ
The Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lewis
Jason S
JS
Kim
Joonyoung
J
Sharp
Terry L
TL
Dence
Carmen S
CS
Gropler
Robert J
RJ
Herrero
Pilar
P
D019342:Acetic Acid / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003326:Coronary Circulation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005240:Feasibility Studies; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D010104:Oxygen Radioisotopes; D019308:Palmitic Acid / Q000378:metabolism*; D049268:Positron-Emission Tomography; D051381:Rats; D011924:Rats, Zucker; D014867:Water / Q000378:metabolism
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010104:Oxygen Radioisotopes; D014867:Water; D019308:Palmitic Acid; D005947:Glucose; D019342:Acetic Acid