Assessing skeletal muscle glucose metabolism with positron emission tomography

Insulin has a marked effect to stimulate the transport and metabolism of glucose in skeletal muscle in healthy individuals, whereas an impaired response, termed insulin resistance, is a major risk factor for diabetes mellitus and other metabolic diseases. Studies of the molecular physiology of insulin action in skeletal muscle indicate that a principal loci of control resides within the proximal steps of glucose transport and phosphorylation. Deoxyglucose, the metabolism of which is limited to these proximal steps, is widely used for in vitro studies of insulin action on glucose transport. The technologies of PET imaging provide a unique opportunity to carry out similar studies in vivo in human skeletal muscle. In this instance, a short-lived positron labeled tracer, [18F] FDG, can be given at sufficiently high specific activity to image not only glucose uptake, but by dynamic PET imaging, by monitoring the time course of [18F] FDG tissue activity, data can be generated to examine the kinetics of glucose transport and phosphorylation. The experimental procedures of this approach, including an overview of the mathematical modeling, are described in this review, along with some of the key findings of the initial applications of PET for the study of glucose metabolism in human skeletal muscle.