Considered for decades as a contaminant of insulin preparations, gluca
gon was among the very first hormones to be isolated, purified, sequen
ced, and synthesized during the late 1950s. The field of glucagon rese
arch exploded after R.H. Unger and his colleagues in Dallas, TX, descr
ibed a method permitting its measurement in the plasma by radioimmunoa
ssay. Such assay made it possible to firmly establish the basic princi
ples of glucagon physiology and to discover its pathophysiology. More
recently, important progress has been made in exploring the molecular
biology of this hormone: the glucagon gene and the glucagon-receptor g
ene have been identified and their expression investigated. Furthermor
e, the processing of the glucagon gene product has been elucidated and
the function of the members of the glucagon family has been clarified
. Finally, current investigations are in progress to develop glucagon
agonists and antagonists and to identify new modes of administration o
f the hormone. These various topics will be considered in this review.