Circulating levels of glucagon-like peptide-2 in human subjects with inflammatory bowel disease.
Glucagon-like peptide-2 (GLP-2) is a recently characterized intestine-derived peptide that exerts trophic activity in the small and large intestine. Whether circulating levels of GLP-2 are perturbed in the setting of human inflammatory bowel disease (IBD) remains unknown. The circulating levels of bioactive GLP-2-(1-33) compared with its degradation product GLP-2-(3-33) were assessed using a combination of RIA and HPLC in normal and immunocompromised control human subjects and patients hospitalized for IBD. The activity of the enzyme dipeptidyl peptidase IV (DP IV), a key determinant of GLP-2-(1-33) degradation was also assessed in the plasma of normal controls and subjects with IBD. The circulating levels of bioactive GLP-2-(1-33) were increased in patients with either ulcerative colitis (UC) or Crohn's Disease (CD; to 229 +/- 65 and 317 +/- 89%, P < 0.05, of normal, respectively). Furthermore, the proportion of total immunoreactivity represented by intact GLP-2-(1-33), compared with GLP-2-(3-33), was increased from 43 +/- 3% in normal healthy controls to 61 +/- 6% (P < 0.01) and 59 +/- 2% (P < 0.01) in patients with UC and CD, respectively. The relative activity of plasma DP IV was significantly reduced in subjects with IBD compared with normal subjects (1.4 +/- 0.3 vs. 5.0 +/- 1.1 mU/ml, respectively; P < 0.05). These results suggest that patients with active IBD may undergo an adaptive response to intestinal injury by increasing the circulating levels of bioactive GLP-2-(1-33), facilitating enhanced repair of the intestinal mucosal epithelium in vivo.
Xiao
Q
Q
Department of Physiology, Mount Sinai Hospital and the Toronto General Hospital, Toronto M5G 2C4, Ontario, Canada M5S 1A8.
Boushey
R P
RP
Cino
M
M
Drucker
D J
DJ
Brubaker
P L
PL
D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D003093:Colitis, Ulcerative / Q000097:blood*; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood*; D005260:Female; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis / Q000097:blood* / Q000276:immunology; D011863:Radioimmunoassay; D012778:Short Bowel Syndrome / Q000097:blood
D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides