Changes in glucagon kinetics and processing in patients with acute pancreatitis

Aim

The kinetics of the pancreatic hormone glucagon in patients with acute pancreatitis have not been investigated as carefully as those of insulin, in spite of its crucial influence on energy metabolism. In the present study, we studied the kinetics of glucagon and glucagon-related peptides assessed by radio-immunoassay. Furthermore, the molecular forms of these peptides were examined using gel filtration chromatography, and the glucagon processes in the pancreas and intestine in the early stage in patients with acute pancreatitis were investigated.

Methodology

Fourteen patients with acute pancreatitis were enrolled in this study. Eight had severe pancreatitis (group S) and six had mild pancreatitis (group M). Ten healthy volunteers were also enrolled as normal controls (group C). Serum levels of glucagon and glucagon-related peptides were assessed on the second admission day in groups S and M, and in an early morning fasting state in group C, using glucagon nonspecific N-terminal (glucagon-like immunoreactivity [GLI]) and specific C-terminal (immunoreactive glucagon [IRG]) radioimmunoassays. The molecular forms of these peptides were also estimated using gel filtration chromatography. We then discuss the glucagon processes based on these findings.

Results

Serum GLI and IRG in groups S and M were significantly higher than those of group C (P < 0.01), while those in group S were also significantly higher than those in group M (P < 0.05). In all patients in groups S and M, except for only three in group S, a peculiar glicentin-like peptide (GLLP) (molecular weight about 8000) other than pancreatic glucagon was observed in IRG gel filtration chromatography, which was clearly absent from group C.

Conclusion

The kinetics and processing of glucagon in patients with acute pancreatitis were quite different from those of healthy subjects. In patients with acute pancreatitis, the peculiar processing of glucagon proceeded in the intestine quite differently from ordinary glucagon processing either in the pancreas or in the intestine, generating a peculiar GLLP.