Secretion by glucagonomas of a possible glucagon precursor

Five patients with glucagonomas had elevated plasma levels of total glucagon immunoreactivity. Gel filtrations of these plasma samples on Bio-Gel P30 columns showed that most of the immunoreactivity eluted in the 3,500-(true glucagon) and 9,000-dalton fractions. After the administration of alpha cell effectors, changes in total glucagon immunoreactivity were seen which were accounted for primarily by the 3,500-dalton species, but there were also changes in the 9,000-dalton moiety. Venous effluent plasma from tumors of two subjects contained elevated concentrations of glucagon immunoreactivity in both fractions. When material from both the 3,500- and 9,000-dalton peaks were serially diluted in a glucagon immunoassay, parallel displacement curves were found, suggesting that both have similar or identical antigenic determinants. Thus, with conversion to a neoplastic state, alpha cells of glucagonomas, much like beta cells of insulinomas, may secrete an increased amount of a larger, 9,000-mol wt glucagon species which may be a prohormone.