By enhancing our understanding of the mechanism(s) linking inhibition of glucagon action to expansion of islet cell mass, we may improve our ability to mitigate the negative side effects of GCGR antagonism while leveraging its favorable effects, including the possibility for beta cell regeneration therapies relying upon delta (and/or alpha) cell reprogramming in T1D and T2D [26,28,29]. Here, GCG is linked to type 2 diabetes mellitus.