A large body of research over the past 50 years demonstrates that the “primary defect” (DeFronzo and Tripathy, 2009) driving T2DM is a decrement in skeletal muscle-cell insulin sensitivity leading to both peripheral and central insulin resistance (DeFronzo, 1988; Shulman et al., 1990; DeFronzo et al., 1992; Holloszy, 2005; DeFronzo and Tripathy, 2009). Here, INS is linked to type 2 diabetes mellitus.