Glucagon in Human Endocrine and Exocrine Disorders

Abstract

In 1972, I prepared an article entitled “Pancreatic alpha-cell function in miscellaneous clinical disorders” (Lawrence 1972). In that chapter it was noted that, despite the enthusiastic search for and desire to implicate abnormalities of pancreatic glucagon secretion in the cause of certain human diseases, with the exception of the glucagonoma syndrome, glucagon’s causal role in other diseases remained elusive. A decade later, it is still uncertain whether abnormally high levels of measured glucagon in the blood of some individuals with, for example, acromegaly, hyperparathyroidism, or pheochromocytoma, reflect a general endocrine hypersecretory state akin to what has been described in the multiple endocrine neoplasia (MEN) syndrome or whether glucagon contributes causally to such endocrinopathies. Inrpretive uncertainties arise, in some part, from our less than perfect ability to measure pancreatic glucagon in bodily fluid or from our inability to interpret accurately what such measurements actually reflect in terms of the pathogenesis of associated disease entities in humans. As an example, radioimmunoassay measurements of glucagon from peripheral blood provide glucagon measurements after substantial hepatic extraction (see Chap. 40) and, in general, measure glucagon of several origins (see Chap. 11). In what follows, however, an attempt has been made to update previous observations which appear to involve glucagon in disordered endocrine and exocrine physiology.