Pancreatic and intestinal processing of proglucagon in man.
We developed antisera and radioimmunoassays against synthetic replicas of glucagon-like peptide-1 (1-36) and -2, predicted products of the glucagon precursor, and against glucagon-like peptide-1 (7-36) identical to the sequence of glucagon-like peptide-1, but lacking its first six N-terminal amino acids. With these tools, we studied the localisation and molecular nature of glucagon-like immunoreactivity in human pancreas, small intestine and plasma. By immunohistochemistry glucagon-like peptide-1, and glucagon-like peptide-2 immunoreactivity coexisted with glucagon in pancreatic islet cells and with enteroglucagon in small intestinal enteroglucagon-producing cells. By chromatography of tissue extracts we found that glucagon-like peptide-1 and glucagon-like peptide-2-immunoreactivities in the human pancreas (307 +/- 51 and 107 +/- 37 pmol/g tissue) were mainly contained in a large peptide, whereas in the small intestine glucagon-like peptide-1 and glucagon-like peptide-2 immunoreactivities were found in separate smaller molecules (49 +/- 21 and 77 +/- 28/g tissue). By isocratic high pressure liquid chromatography of the large pancreatic glucagon-like peptide we found that this peptide is heterogeneous. By chromatographic analysis glucagon-like peptide-1 immunoreactivity in fasting plasma was mainly found in a large peptide corresponding to the pancreatic form, while after a meal a smaller molecular form coeluting by gel filtration with glucagon-like peptide-1 predominated.
Orskov
C
C
Institute of Medical Physiology C, University of Copenhagen, Denmark.
Holst
J J
JJ
Poulsen
S S
SS
Kirkegaard
P
P
D000328:Adult; D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005768:Gastrointestinal Hormones / Q000032:analysis*; D005934:Glucagon / Q000032:analysis* / Q000097:blood; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D006801:Humans; D007082:Ileum / Q000032:analysis; D007421:Intestine, Small / Q000032:analysis*; D010179:Pancreas / Q000032:analysis*; D010187:Pancreatic Hormones / Q000032:analysis*; D010455:Peptides / Q000032:analysis* / Q000097:blood; D052336:Proglucagon; D011498:Protein Precursors / Q000032:analysis* / Q000097:blood; D011863:Radioimmunoassay
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D010187:Pancreatic Hormones; D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon