Given the increasing appreciation of glucagon’s central role in the etiology of diabetes (Burcelin et al., 1996; Johnson et al., 1982; Lee et al., 2012; Patil et al., 2020; Unger & Cherrington, 2012; Wewer Albrechtsen et al., 2019), resolving persistent uncertainties and establishing its true mechanism of action in health and disease are now more urgent than ever.1 Here, GCG is linked to diabetes mellitus.