Challenging the Paradigm: Training-Induced increase in Insulin Sensitivity in Equine Athletes is correlated with downregulation of insulin dependent glucose transporters

In human athletes, training-induced improvements in insulin sensitivity typically coincide with increased GLUT4 expression and a glucose-centric fuel strategy. In horses, recent studies show the opposite: training is associated with reduced total GLUT4/GLUT12 abundance, challenging the assumption that enhanced glucose transport underpins improved insulin sensitivity. This study examined how insulin-dependent glucose transporters relate to insulin sensitivity in trained horses. After eight weeks of standardized aerobic harness training, horses displayed a more efficient insulin economy during an oral glucose tolerance test, with reduced peak insulin, lower insulin AUC, and a delayed time to peak. Intravenous glucose tolerance indices did not show corresponding improvements. Total GLUT4 and GLUT12 decreased with training, most clearly in acute post-exercise samples. Acute GLUT12 correlated positively with peak and total insulin responses, and its training-induced decline correlated with increased insulin time-to-peak. These data indicate that horses improve insulin sensitivity without upregulating or even downregulating GLUT4/GLUT12. This supports the emerging concept that equine training shifts insulin’s primary role toward non-glucose substrates (e.g., amino-acid–supported anaplerosis, lipid oxidation, microbiome-derived fuels). OGTT-type tests may be more sensitive to training adaptations than intravenous tests, and nutrition should support this shifted insulin profile with adequate amino acids, forage-first feeding, and moderated starch.