Influence of dietary state and insulin on myocardial, skeletal muscle and brain [F-18]-fluorodeoxyglucose kinetics in mice

Background: We evaluated the effect of insulin stimulation and dietary changes on myocardial, skeletal muscle and brain [F-18]-fluorodeoxyglucose (FDG) kinetics and uptake in vivo in intact mice. Methods: Mice were anesthetized with isoflurane and imaged under different conditions: non-fasted (n = 7; controls), non-fasted with insulin (2 IU/kg body weight) injected subcutaneously immediately prior to FDG (n = 6), fasted (n = 5), and fasted with insulin injection (n = 5). A 60-min small-animal PET with serial blood sampling and kinetic modeling was performed. Results: We found comparable FDG standardized uptake values (SUVs) in myocardium in the non-fasted controls and non-fasted-insulin injected group (SUV 45-60 min, 9.58 +/- 1.62 vs. 9.98 +/- 2.44; p = 0.74), a lower myocardial SUV was noted in the fasted group (3.48 +/- 1.73; p < 0.001). In contrast, the FDG uptake rate constant (K-i) for myocardium increased significantly by 47% in non-fasted mice by insulin (13.4 +/- 3.9 ml/min/100 g vs. 19.8 +/- 3.3 ml/min/100 g; p = 0.030); in fasted mice, a lower myocardial Ki as compared to controls was observed (3.3 +/- 1.9 ml/min/100 g; p < 0.001). Skeletal muscle SUVs and K-i values were increased by insulin independent of dietary state, whereas in the brain, those parameters were not influenced by fasting or administration of insulin. Fasting led to a reduction in glucose metabolic rate in the myocardium (19.41 +/- 5.39 vs. 3.26 +/- 1.97 mg/min/100 g; p < 0.001), the skeletal muscle (1.06 +/- 0.34 vs. 0.34 +/- 0.08 mg/min/100 g; p = 0.001) but not the brain (3.21 +/- 0.53 vs. 2.85 +/- 0.25 mg/min/100 g; p = 0.19). Conclusions: Changes in organ SUVs, uptake rate constants and metabolic rates induced by fasting and insulin administration as observed in intact mice by small-animal PET imaging are consistent with those observed in isolated heart/muscle preparations and, more importantly, in vivo studies in larger animals and in humans. When assessing the effect of insulin on the myocardial glucose metabolism of non-fasted mice, it is not sufficient to just calculate the SUV - dynamic imaging with kinetic modeling is necessary.