Circulating levels of glucagon-like peptide-2 in human subjects with inflammatory bowel disease

Abstract

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.