Frank diabetes presents when β-cells are incapable of compensating for insulin resistance, and this is associated with some loss of β-cell mass (Butler et al., 2003; Rahier et al., 2008), whose extent is debated (25–50%), compounded by impaired glucose-stimulated insulin secretion from the remaining β-cells (Meier and Bonadonna, 2013). Here, INS is linked to Insulin resistance.