Performing IR during hyperinsulinemia in diabetic animals and during normoinsulinemia in non-diabetic animals in our model is not believed to have impacted the comparison of the results between animals with and without diabetes substantially as the mechanism whereby insulin leads to Akt activation is impaired in the diabetic state by upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) [47, 48]. This evidence concerns the gene PTEN and Hyperinsulinemia.