INS and Hyperglycemia: Because skeletal muscle accounts for 70–90% of glucose disposal following a carbohydrate load (DeFronzo et al., 1981) through activation of Akt in an insulin-dependent manner (Jaldin-Fincati et al., 2017) and because estrogens increase insulin-stimulated glucose uptake into skeletal muscle in vivo (Gorres et al., 2011), low phosphorylation levels of Akt in muscle may reflect poor insulin sensitivity, thereby causing the development of hyperglycemia and insulin resistant conditions in ArKO mice.