Dexamethasone-induced insulin resistance: kinetic modeling using novel PET radiopharmaceutical 6-deoxy-6-[(18)F]fluoro-D-glucose.

PURPOSE

An insulin-resistant rat model, induced by dexamethasone, was used to evaluate a Michaelis-Menten-based kinetic model using 6-deoxy-6-[(18)F]fluoro-D-glucose (6-[(18)F]FDG) to quantify glucose transport with PET.

PROCEDURES

Seventeen, male, Sprague-Dawley rats were studied in three groups: control (Ctrl), control + insulin (Ctrl + I), and dexamethasone + insulin (Dex + I). PET scans were acquired for 2 h under euglycemic conditions in the Ctrl group and under hyperinsulinemic-euglycemic conditions in the Ctrl + I and Dex + I groups.

RESULTS

Glucose transport, assessed according to the 6-[(18)F]FDG concentration, was highest in skeletal muscle in the Ctrl + I, intermediate in the Dex + I, and lowest in the Ctrl group, while that in the brain was similar among the groups. Modeling analysis applied to the skeletal muscle uptake curves yielded values of parameters related to glucose transport that were greatest in the Ctrl + I group and increased to a lesser degree in the Dex + I group, compared to the Ctrl group.

CONCLUSION

6-[(18)F]FDG and the Michaelis-Menten-based model can be used to measure insulin-stimulated glucose transport under basal and an insulin resistant state in vivo.