GCGR and diabetes mellitus: Collectively, these observations indicate that the lack of glucagon signaling is not sufficient per se to prevent severe hyperglycemia and diabetes following extreme β-cell loss, and contrast with previous studies in which Gcgr-/-, or anti-GCGR-treated mice did not develop the metabolic manifestations of the disease when β-cell ablation was mediated by STZ (Conarello et al., 2006; Lee et al., 2011; 2012; Wang et al., 2015).