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-deriv ed peptide that exerts trophic activity in the small and large intestine. W hether circulating levels of GLP-2 are perturbed in the setting of human in flammatory bowel disease (IBD) remains unknown. The circulating levels of b ioactive GLP-2-(1-33) compared with its degradation product GLP-2-(3-33) we re assessed using a combination of RIA and HPLC in normal and immunocomprom ised control human subjects and patients hospitalized for IBD. The activity of the enzyme dipeptidyl peptidase TV (DP IV), a key determinant of GLP-2- (1-33) degradation was also assessed in the plasma of normal controls and s ubjects with IBD. The circulating levels of bioactive GLP-2-(1-33) were inc reased in patients with either ulcerative colitis (UC) or Crohn's Disease ( CD; to 229 +/- 65 and 317 +/- 89%, P < 0.05, of normal, respectively). Furt hermore, the proportion of total immunoreactivity represented by intact GLP -2-(1-33), compared with GLP-2-(3-33), was increased from 43 +/- 3% in norm al healthy controls to 61 +/- 6% (P < 0.01) and 59 +/- 2% (P < 0.01) in pat ients with UC and CD, respectively. The relative activity of plasma DP IV w as 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.