We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78–107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110±14 pmol/liter (mean±SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43±11%, in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16±2 min to 30±5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47±17% and 40±9%, during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 ±0.2 versus 3.7±0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.

Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man.

RELEASING factors1 and other brain peptides2 have been the subject of extensive studies and the high sensitivity of modern measurement techniques has led to the discovery, in various tissues3,4 and in the nervous system5–9, of new, unpredicted locations for otherwise well known peptides. Evidence for the presence in the vertebrate nervous system of a hitherto undescribed brain gastrin immunoassayable peptide (BGP) is presented here.

New peptide in the vertebrate CNS reacting with antigastrin antibodies.

We developed specific antibodies and RIAs for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), two predicted products of the glucagon gene, and studied the occurrence, nature, and secretion of immunoreactive GLP-1 and GLP-2 in pig pancreas and small intestine Immunoreactive GLP-1 and GLP-2 were identified in glucagon-producing cells of the pancreatic islets, and in glicentin-producing cells of the small intestine Immunoreactive GLP-1 and 2 in intestinal extracts corresponded in molecular size to peptides synthesized according to the predicted structure By reverse phase HPLC, intestinal and synthetic GLP-1 behaved similarly, whereas synthetic and intestinal GLP-2 differed Pancreatic extracts contained a large peptide with both GLP-1 and GLP-2 immunoreactivity Secretion was studied using isolated perfused pig pancreas during arginine stimulation, and isolated perfused pig ileum during either luminal glucose stimulation or vascular administration of the neuropeptide, gastrin-releasing peptide (GRP) Im

Glucagon-Like Peptides GLP-1 and GLP-2, Predicted Products of the Glucagon Gene, Are Secreted Separately from Pig Small Intestine but Not Pancreas

We studied the effect of truncated glucagon-like peptide-1 [naturally occurring GLP-1; proglucagon-(78–107) amide], a potent insulinotropic peptide from the pig ileum, on endocrine and exocrine secretion of potential gastrointestinal target organs using isolated perfused preparations of the porcine pancreas, antrum, and nonantral part of the stomach. Truncated GLP-1 significantly increased somatostatin secretion from the pancreas at 10-10 mol/liter and more than doubled the secretion at 1O-9 mol/liter, but had no effect on either somatostatin or gastrin secretion from the antrum or on somatostatin secretion from the nonantral stomach in concentrations up to 10-8 mol/ liter. Insulin secretion from the pancreas (with 7 mmol/liter glucose in the perfusate) increased 2-fold with truncated GLP-1 at 10-10 mol/liter and almost 5-fold at 10-9 mol/liter. Pancreatic glucagon secretion was inhibited by 50% at 10-10 mol/liter and by 70–80% at 10-9 mol/liter. Full-length GLP-1 [proglucagon- (72–107)] and GLP-2 [proglu...

J F Rehfeld

Papers

Determination of gastrin in serum. An evaluation of the reliability of a radioimmunoassay.