Our recent description of a novel human disease (Mahvash disease) with hyperglucagonemia, α cell hyperplasia, and pancreatic neuroendocrine tumors (PNETs) associated with a homozygous inactivating GCGR mutation suggests that the pancreata of mice and humans may respond similarly to glucagon signaling inhibition [18], [19]. Here, GCGR is linked to GCGR-related hyperglucagonemia.