Evidence for Transformation of Glucagon-Like Immunoreactivity of Gut into Pancreatic Glucagon In Vivo

Abstract

SUMMARYThe 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 < 0.05) and increased until the end of the infusion (90th min, 218 ± 60 pg/ml; P < 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. DIABETES 30:792-794, September 1981. R ecently data have been accumulated pointing to the similarities of pancreatic glucagon derived from the A-cells of the pancreas and the stomach, and enteric glucagon-like immunoreactivity (GLI) produced by the L-cells of the gut, and raising the possibility of a common biosynthetic precursor. One of the components of gut GLI, the 100-amino acid polypeptide, glicentin, has been shown to contain the full sequence of glucagon, extended from the C-terminus by an additional 8-amino acid chain and from the N-terminus by a 63 amino-acid chain.

Circulating glucagon after total pancreatectomy in man

“…Possibly, the two components identified in plasma from pancreatectomized patients are identical to the forms found in human tissue extracts. However, the presence in plasma of these components with C-terminal immunoreactivity might also be due to hydrolysis within the circulation of the components with C-terminal extensions as suggested by Korany et al [20]. This mechanism might also explain the initial increase in the concentration of C-terminal immunoreactivity, which coincided with the peak of the 6-15 immunoreactivity response to the test meal.…”

Gut and Pancreatic Hormones after Jejunoileal Bypass with 3:1 or 1:3 Jejunoileal Ratio

“…A similar and corro borating result has been obtained by Besterman et al [21] who found an excessive postcibal release of enteroglucagon in coeliac dis ease in which the ileum is hypertrophied and exposed to a large amount of unabsorbed food. The enteroglucagon molecule contains the entire sequence of 'pancreatic' glucagon [22,23] and may be a precursor of glucagon in the islet cells [24], Furthermore, there is some evidence that the circulating enteroglu cagon may act as such precursor [25]. It is still unknown what the function of circulating enteroglucagon is.…”

“…The continuing increase after the meal in the bypass patients may reflect a cor responding secretion, the reason for which could be deinhibition because of the low glu cose levels, but another possibility is that a small fraction of the large amount of circula tion enteroglucagon has been broken down to fragments reacting in the assay [25], PP is secreted from pancreas under con trol of the vagal, cholinergic system [5], It was not expected that the bypass operation influences the PP secretion, and this was con firmed by our results as well as by those of Sarson et al [1], They found a severe reduc tion of the PP response after biliopancreatic bypass, which involves a partial gastrectomy and a long Roux-en-Y gastroenterostomy. The reduction is probably due to damage of vagal fibres to the pancreas.…”

Pattern of Cell Proliferation and Enteroglucagon Response following Small Bowel Resection in the Rat

“…Studies in man [26] suggest that neither of these possibilities makes a significant contribution to plasma enteroglucagon estimates. Although Koranyi et al [27] have shown conversion of glucagon-like immunoreactivity to immunoreac tive glucagon in the circulation, our chro matographic studies provide no evidence of a major degree of such interconversion in the rat, as only the Kav 0.25 molecular form of glucagon-like immunoreactivity is signifi cantly elevated. Smaller forms of glucagon like immunoreactivity in the Kav 0.58 peak seem only to have undergone a minor non significant degree of elevation in the resected rats.…”