Glucagon receptor as a drug target: A witches' brew of eye of newt (peptides) and toe of frog (receptors)

Glucagon has a noble history in the annals of metabolic disease (1), even though to a layperson insulin is its more famous counter-regulatory partner. For decades medical students have been taught that glucagon raises blood glucose by increasing hepatic glucose output and that alleviation of hypoglycemia is its primary function (2). Thus, inhibition of glucagon secretion (3) or action (4) are logical approaches to the development of therapeutics that improve glycemic control in both type 2 and type 1 diabetes mellitus; indeed, this strategy has been pursued for nearly 4 decades.