Amidated and non-amidated glucagon-like peptide-1 (GLP-1): non-pancreatic effects (cephalic phase acid secretion) and stability in plasma in humans.
The incretin and enterogastrone hormone, GLP-1, occurs in an amidated (GLP-1 (7-36) amide; 75%) and a glycine-extended (GLP-1 (7-37); 25%) form. Their effects on the endocrine pancreas are similar and their overall (mainly renal) elimination rates appear to equal. Assuming that they might differentially affect non-pancreatic targets we investigated the effect of GLP-1 (7-37) infused at 0.7 pmol/kg/min on sham-feeding induced acid secretion in six healthy volunteers. The infusion increased the plasma concentrations from 16+/-2 pmol/l to 45+/-2 pmol/l. This was associated with a 61+/-14% decrease in acid output compared to saline and was not significantly different from that previously observed with GLP-1 (7-36) amide infused at the same rate. We then compared the degradation of the two forms in human plasma at 37 degrees C in vitro. T1/2 values were 32+/-3 (7-37) and 42+/-2 min (7-36) amide (P=0.007). The difference in metabolism persisted after addition of diprotin A, an inhibitor of dipeptidyl peptidase IV, the enzyme responsible for the initial degradation of GLP-1 in plasma, and broader enzyme inhibitors. Thus, the only effect of the amidation of GLP-1 seems to be to enhance its survival in plasma.
Wettergren
A
A
Department of Surgical Gastroenterology C, Rigshospitalet, Copenhagen, Denmark.
Pridal
L
L
Wøjdemann
M
M
Holst
J J
JJ
D000328:Adult; D001414:Bacitracin / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D013270:Stomach / Q000187:drug effects*
D009842:Oligopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D001414:Bacitracin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C041445:diprotin A