Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans.
Using specific radioimmunoassays, we studied the occurrence of amidated and glycine-extended glucagon-like peptide I (GLP-I) molecules in the human small intestine and pancreas and in the circulation system in response to a breakfast meal. Through gel permeation chromatography of extracts of the human pancreas (n = 5), we found that 71% of the GLP-I immunoreactivity eluted as a large molecule corresponding to the major proglucagon fragment, 24% corresponded to GLP-I 1-36 amide, and 5% to GLP-I 1-37. By gel permeation chromatography of extracts of human small intestine (n = 6), we found that all immunoreactivity eluted in one peak at the common elution position of the two insulin-releasing peptides, GLP-I 7-36 amide and GLP-I 7-37. Of the GLP-I immunoreactivity, 80% corresponded to GLP-I 7-36 amide and 20% to GLP-I 7-37. The mean concentrations of amidated GLP-I and glycine-extended GLP-I in fasting plasma were 7 +/- 1 and 6 +/- 1 pM, respectively (n = 6). In response to a breakfast meal, the concentration of amidated GLP-I rose significantly amounting to 41 +/- 5 pM 90 min after the meal ingestion, whereas the concentration of glycine-extended GLP-I only rose slightly to a maximum of 10 +/- 1 pM. Thus, both amidated and glycine-extended GLP-I molecules are produced in the small intestine and in the pancreas in humans. Both amidated and glycine-extended GLP-I are measurable in fasting plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Orskov
C
C
Department of Medical Anatomy, Panum Institute, Copenhagen, Denmark.
Rabenhøj
L
L
Wettergren
A
A
Kofod
H
H
Holst
J J
JJ
D000328:Adult; D002850:Chromatography, Gel; D004435:Eating; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000032:analysis* / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000737:chemistry* / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000737:chemistry* / Q000166:cytology; D010446:Peptide Fragments / Q000032:analysis* / Q000097:blood* / Q000302:isolation & purification; D052336:Proglucagon; D011498:Protein Precursors / Q000032:analysis* / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D010446:Peptide Fragments; D011498:Protein Precursors; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon