Caloric restriction treatment (30−50%) in rodent models of diabetes (i.e., db/db, aged mice or Zucker diabetic fatty rat) improves glucose tolerance and insulin sensitivity (Colombo et al., 2006; Kanda et al., 2015; Sheng et al., 2016; Rosa et al., 2018), β-cell mass (Ohneda et al., 1995; Bates et al., 2008; He et al., 2012; Kanda et al., 2015) and insulin secretion (Ohneda et al., 1995; Colombo et al., 2006; He et al., 2012; Kanda et al., 2015; Figure 5). This evidence concerns the gene INS and diabetes mellitus.