The contribution of basal P-GCG to support postabsorptive or fasting euglycemia has been extensively investigated in mice and rats with and without diabetes using a chronic blockade of glucagon signaling by treating with a GCGR inhibitor (24, 39–41), GCG gene deletion (42–50), α cell ablation (44, 47, 50, 51), or an immune-neutralization of P-GCG (47, 52), as well as an acute blockade of glucagon signaling by an immune-neutralization of P-GCG (53–61) (Table 3). This evidence concerns the gene GCGR and diabetes mellitus.