Deficiency of the intestinal growth factor, glucagon-like peptide 2, in the colon of SCID mice with inflammatory bowel disease induced by transplantation of CD4+ T cells.
BACKGROUND
Glucagon-like peptide 2 (GLP-2) is produced in endocrine L-cells of the intestinal mucosa. Recently, GLP-2 was found to stimulate intestinal mucosal growth. Our objective was to study the content of GLP-2 in the large intestine in a murine model of T-cell-induced inflammatory bowel disease.


METHODS
Inflammation was induced by adoptive transfer of CD4+ blast T cells from BALB/c mice to SCID mice. The amount of GLP-2 (1-33) was measured with a specific, NH2-terminally directed radioimmunoassay in tissue extracts from the large intestine of transplanted mice developing colitis and from BALB/c and SCID control mice.


RESULTS
In the middle and descending colon segments showing the most severe signs of inflammatory lesions in the CD4+ T-cell-transplanted mice, the amount of GLP-2 was significantly lower than in similar colon segments in both untransplanted SCID mice and normal BALB/c mice (P = 0.0013 and 0.0033). In the descending colon the amount of GLP-2 was 6.7 +/- 1.0 pmol/g protein in the CD4+ transplanted mice compared with 68.4 +/- 20.3 and 42.7 +/- 4.3 in the two groups of control mice. Similar findings were made with regard to the contents of the two other proglucagon-derived intestinal peptides, glicentin and GLP-1.


CONCLUSIONS
The amount of GLP-2 is markedly reduced in the colon of mice with a T-cell-induced inflammatory bowel disease histopathologically resembling both Crohn disease and ulcerative colitis. This observation may provide a pathophysiologic rationale for administration of GLP-2 as a trophic factor in inflammatory bowel disease.
Schmidt
P T
PT
Dept. of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark.
Hartmann
B
B
Bregenholt
S
S
Hoist
J J
JJ
Claesson
M H
MH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D005934:Glucagon / Q000172:deficiency*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006133:Growth Substances / Q000172:deficiency*; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D010446:Peptide Fragments / Q000172:deficiency*
D053767:Glucagon-Like Peptide 2; D006133:Growth Substances; D010446:Peptide Fragments; D004763:Glucagon-Like Peptides; D005934:Glucagon