INS and metabolic disease: Insulin/IGF-1 signaling has been shown to regulate mitochondrial DNA and OXPHOS protein syntheses, oxidative capacity, and ATP production and dysregulation in insulin signaling is associated with mitochondrial dysfunction that leads to various metabolic diseases (Kelley et al., 2002; Lowell and Shulman, 2005), although the causal relationship between insulin resistance and mitochondrial dysfunction remains to be further defined (Turner and Heilbronn, 2008).