Evidence for transformation of glucagon-like immunoreactivity of gut into pancreatic glucagon in vivo.

The effect of gut glucagon-like immunoreactivity (GLI) devoid of pancreatic glucagon was studied in piglets. All glucagon-like peptides with an accessible C-terminal were removed from the gut extract by specific antibodies reacting with the C-terminal of the glucagon molecule. Endogenous secretion of pancreatic and gut glucagon was blocked by somatostatin infusion, and then the purified gut glucagon preparation was infused. The latter prevented the hypoglycemia resulting from somatostatin infusion, and increased the glucagon level detectable by C-terminal specific antibodies in the blood of the animals. This rise was significant statistically from the 30th min of GLI administration (26.7 +/- 7.2 pg/ml versus 137.0 +/- 67.0 pg/ml; P less than 0.05) and increased until the end of the infusion (90th min, 218 +/- 60 pg/ml; P less than 0.005). It has been suggested that, owing to the in vivo enzymatic degradation of the infused gut glucagon, biologically active "pancreatic" glucagon fractions are formed extracellularly.