Immunologic characterization of plasma glucagon components in a patient with malignant glucagonoma

Plasma immunoreactive glucagon (IRG) components were analyzed by gel filtration on either a Bio-Gel P-30 or a Sephadex G-150 column (1.0 X 68 cm) in a 47-year-old male with biopsy-proven malignant glucagonoma. Plasma samples were obtained before and after 20 courses of streptozotocin treatment as well as after administration of a somatostatin-derivative (SRIF-D, 0.38 mg, subcutaneous), regular insulin (0.2 U/kg, intravenous), and secretin (2 U/kg, intravenous). The fractions from the columns were assayed for IRG by simultaneous radioimmunoassay with C-terminal (Unger 30 K) and N-terminal (OAL 196) antibodies to glucagon. Four IRG components were observed. The largest had a molecular weight of approximately 150,000 daltons and cross-reacted much more strongly with the N-terminal antibody than with the C-terminal. The second IRG component appeared to be about 9000 daltons and cross-reacted more strongly with the N-terminal antibody. The third and major IRG component comprised 51.8% to 88.1% of the total IRG as measured with C-terminal antibody, corresponded in molecular weight to synthetic 3500 dalton glucagon, and reacted roughly equally with each of the two antibodies. The fourth IRG component cross-reacted only with N-terminal antibody and appeared to be smaller than 3500 daltons. The plasma IRG level decreased from 8829 pg/mL to 1421 pg/mL (averages of five consecutive determinations) after 20 courses of treatment with streptozotocin with significant clinical improvement. A marked (74%) but transient decrease in plasma IRG was observed after the SRIF-D injection, whereas secretion and insulin caused increases in plasma IRG level of 53% and 22%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)