The year 2023 marks 100 years since publication of the first report of a hyperglycemic factor in pancreatic extracts which CP Kimball and John R Murlin named glucagon (from GLUCose AGONist). Glucagon has a range of profound effects on metabolism including, but not limited to, stimulation of hepatic glucose production. Dysregulation of glucagon secretion is a key feature of both major forms of diabetes, leading to the concept that diabetes is a bihormonal disorder. Still, work to fully understand the production and biological effects of glucagon has proceeded at a slower pace compared to that of insulin. A recent resurgence of interest in the islet α cell, the predominant site of glucagon production, has been facilitated in part by technological innovations. This work has led to significant developments in the field, from defining how alpha cells develop, how glucagon is secretion from pancreatic alpha cells is regulated, through to determining the role of glucagon in metabolic homeostasis and the progression of both major forms of diabetes. In addition, glucagon is considered to be a promising target for diabetes therapy, with many new potential applications arising from research in this field. This collection of reviews, led by Guest Editors James Cantley, Rebecca Hull-Meichle and Vincent Poitout, is intended to capture the field’s current understanding of glucagon and alpha cell biology, as well stimulate additional interest and research on this important hormone.
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