Using whole-body metabolic phenotyping and molecular characterization, we show that, while milk protein and Leu have protective metabolic effects, Val induces a disturbance in glucose tolerance, which is driven in part by persistently elevated circulating 3-HIB levels mediating a skeletal muscle IR by driving basal glucose uptake resulting in glucotoxicity inhibition of AKT signaling, findings confirmed with in vitro studies. Here, AKT1 is linked to glucose measurement.