Size heterogeneity of immunoreactive glucagon during bile-duct obstruction in the rabbit

The influence of bile-duct obstruction upon basal plasma glucagon levels and the relationship between glucagon-like substance in bile and postobstructive plasma glucagon were examined in the rabbit. Immunoreactive glucagon (IRG) was measured with antiserum 30 K (Unger). Bile-duct obstruction was followed by a prompt rise within 60 minutes in plasma IRG which was four times the basal value, but had little influence on plasma immunoreactive insulin and blood sugar. The biliary IRG and the elevated plasma IRG during bile-duct obstruction were filtered with a Bio-Gel P-10 column. Most of the postobstructive plasma IRG appeared in the void volume area (plasma large IRG), while almost all of the biliary IRG was recovered in the position equivalent to approximately 2000 daltons (biliary IRG 2000). Both IRGs of different molecular sizes revealed similar dilution curve in radioimmunoassay to that with porcine glucagon. After incubation of bile with preobstructive plasma, the IRG elution profile of the mixture contained an increased amount of large molecular size IRG similar to that of postobstructive plasma in regard to 30K specificity and elution position. The disappearance of IRG in the void volume area was observed when the bile-plasma mixture or the postobstructive plasma was filtered with acidic buffer. These results suggest that plasma large IRG contributing to hyperglucagonemia during bile-duct obstruction may be derived from biliary IRG 2000.