While the role of insulin mediated regulation of glucose homeostasis is well established and the contribution to the pathophysiology of T2D has been extensively quantified (Mari et al., 2002b; Panunzi et al., 2007; Cobelli et al., 2009; Cobelli et al., 2014; Bergman, 2021), the role of glucagon and alpha-cell dysregulation is less well studied from a computational perspective. This evidence concerns the gene INS and type 2 diabetes mellitus.