Four sidenotes about glucagon peptides

Century old glucagon is a classic pancreatic hormone. But today we also know that the glucagon gene is expressed at high levels at extrapancreatic sites - particularly so in the gut. Major hormonal glucagon gene products in the digestive tract are the two glucagon-like peptides (GLP-1 and -2). Of these, truncated GLP-1 has in recent decades attracted massive interest due to its incretin effect, and the subsequent GLP-1 derived design of potent diabetes and obesity drugs. Truncated GLP-1 has consequently become an important contributor to gastrointestinal endocrinology. The gastrointestinal branch of endocrinology today includes more than 100 bioactive peptides encoded by some 30 different hormone genes. Therefore, the gut is the largest endocrine organ in the body. In addition to a general discussion of glucagon peptides in the hierarchy of gut hormones, this review also includes three short notes about glucagon studies from the 1970s. These studies dealt with reactive hypoglycemia, chronic liver disease, and the secretory response of pancreatic glucagon to gastrin/cholecystokinin stimulation. Considering today's possibilities in molecular endocrinology, revisits to the questions raised by these studies might be worthwhile.