In This Issue of Diabetes

Proof-of-principle experiments showing relationship between systemic glucose (top) and tracer kinetics (bottom).The first tracer was given at time 0 and the second after 40 min.2DG, 2-deoxyglucose; DPM, disintegration per minute.Cutler et al.Dual Tracer Test to measure tissue-specific insulin action in individual mice identifies in vivo insulin resistance without fasting hyperinsulinemia.Diabetes 2024;73:359-373 Dual Tracer Test Can Estimate Basal and Insulin-Stimulated Glucose Uptake in the Same MouseA method to quantify both basal and insulin-stimulated glucose uptake in the same mouse is described by Cutler et al. (p.359).Promising to substantially cut the numbers of animals used in experiments, the approach addresses the need for a separate group of animals to measure basal glucose uptake, which can be problematic when trying to quantify insulin action in individual tissues.Called the Dual Tracer Test, the approach involves sequential retroorbital injections of two versions of radiolabeled 2-deoxyglucose separated by 40 min with a maximal dose of insulin given with the second injection.This approach, the authors highlight, means paired basal and insulin-stimulated measures of glucose can be collected and thus used to adjust values to account for the effect of basal glucose on insulin-stimulated glucose uptake.In initial pilot experiments, the authors found the approach was feasible, obtaining expected trajectories of glucose following anesthesia in the mice and injection of the different glucose tracers and insulin.They then validated the method in a classic diet-induced model of insulin resistance and a novel transgenic mouse model with reduced GLUT4 expression."In the rapidly advancing field of metabolism and the use of mouse models, there is a pressing need for simpler, more robust measures of tissue-specific insulin action in this model," said author David E. James."Our goal is to introduce a novel method that could empower laboratories to enhance their metabolic phenotyping capability beyond current methods."While highlighting several strengths of the approach, the authors stress there are still limitations that future users should account for, along with recommended minimum data requirements.Nevertheless, according to James, the approach can be expanded into different mouse strains to look at the impact of genetic backgrounds on phenotypes."We are particularly excited about the potential of the method for studying how genes and the environment interact to determine metabolic phenotypes like insulin sensitivity," he added.