Insulin-stimulated glucose transport in skeletal muscle is regarded as a key determinant of insulin sensitivity, yet isolation of this step for quantification in human studies is a methodological challenge. One notable approach is physiological modeling of dynamic positron emission tomography (PET) imaging using 2-[18-fluoro]2-deoxyglucose ([(18)F]FDG); however, this has a potential limitation in that deoxyglucose undergoes phosphorylation subsequent to transport, complicating separate estimations of these steps. In the current study we explored the use of dynamic PET imaging of [(11)C]3-O-methylglucose ([(11)C]3-OMG), a glucose analog that is limited to bidirectional glucose transport. Seventeen lean healthy volunteers with normal insulin sensitivity participated; eight had imaging during basal conditions, and nine had imaging during euglycemic insulin infusion at 30 mU/min.m(2). Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [(11)C]3-OMG. Spectral analysis of tissue activity indicated that a model configuration of two reversible compartments gave the strongest statistical fit to the kinetic pattern. Accordingly, and consistent with the structure of a model previously used for [(18)F]FDG, a two-compartment model was applied. Consistent with prior [(18)F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [(11)C]3-OMG from plasma to tissue interstitium. However, during insulin infusion, a robust and highly significant increase was observed in the kinetics of inward glucose transport; this and the estimated tissue distribution volume for [(11)C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [(11)C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle.
Quantitative assessment of glucose transport in human skeletal muscle: dynamic positron emission tomography imaging of [O-methyl-11C]3-O-methyl-D-glucose
BERTOLDO, ALESSANDRA;COBELLI, CLAUDIO;
2005
Abstract
Insulin-stimulated glucose transport in skeletal muscle is regarded as a key determinant of insulin sensitivity, yet isolation of this step for quantification in human studies is a methodological challenge. One notable approach is physiological modeling of dynamic positron emission tomography (PET) imaging using 2-[18-fluoro]2-deoxyglucose ([(18)F]FDG); however, this has a potential limitation in that deoxyglucose undergoes phosphorylation subsequent to transport, complicating separate estimations of these steps. In the current study we explored the use of dynamic PET imaging of [(11)C]3-O-methylglucose ([(11)C]3-OMG), a glucose analog that is limited to bidirectional glucose transport. Seventeen lean healthy volunteers with normal insulin sensitivity participated; eight had imaging during basal conditions, and nine had imaging during euglycemic insulin infusion at 30 mU/min.m(2). Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [(11)C]3-OMG. Spectral analysis of tissue activity indicated that a model configuration of two reversible compartments gave the strongest statistical fit to the kinetic pattern. Accordingly, and consistent with the structure of a model previously used for [(18)F]FDG, a two-compartment model was applied. Consistent with prior [(18)F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [(11)C]3-OMG from plasma to tissue interstitium. However, during insulin infusion, a robust and highly significant increase was observed in the kinetics of inward glucose transport; this and the estimated tissue distribution volume for [(11)C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [(11)C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle.
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