TY - JOUR
T1 - Enterotrophic Effects of Glucagon-Like Peptide 2 Are Enhanced by Neurotensin
AU - Litvak, David A.
AU - Evers, B. Mark
AU - Hellmich, Mark R.
AU - Townsend, Courtney M.
PY - 1999/1/1
Y1 - 1999/1/1
N2 - Combination therapy with enterotrophic agents may be useful in patients with the short bowel syndrome. The gut hormones neurotensin (NT) and glucagon-like peptide 2 (GLP-2) are potent enterotrophic factors when administered alone; however, their combined effects are not known. Using a GLP-2-producing tumor (STC-1), we determined whether administration of NT enhances the effect of GLP-2 on intestinal growth. Athymic mice were injected with STC-1 cells (6 × 106) subcutaneously. Twenty-three days after STC-1 implantation, mice received either NT (300 μg/kg or 600 μg/kg) or saline solution (control) subcutaneously three times a day for 6 days. Two groups of tumor-free mice received either saline or NT for 6 days. At sacrifice, jejunum and ileum were collected, weighed, and analysed for DNA and protein content. In the jejunum, NT combined with GLP-2 (from STC-1) increased weight, protein content (markers of mucosal hypertrophy), and DNA content (a marker of mucosal hyperplasia), compared to either NT or GLP-2 alone. In the ileum, the combination of NT and GLP-2 significantly increased weight and/or protein content compared to NT or GLP-2 alone. Administration of NT enhances the enterotrophic effects of GLP-2, augmenting hypertrophy of the entire small bowel and hyperplasia of the jejunum. The combination of NT and GLP-2 may be useful to enhance intestinal growth in patients with the short bowel syndrome.
AB - Combination therapy with enterotrophic agents may be useful in patients with the short bowel syndrome. The gut hormones neurotensin (NT) and glucagon-like peptide 2 (GLP-2) are potent enterotrophic factors when administered alone; however, their combined effects are not known. Using a GLP-2-producing tumor (STC-1), we determined whether administration of NT enhances the effect of GLP-2 on intestinal growth. Athymic mice were injected with STC-1 cells (6 × 106) subcutaneously. Twenty-three days after STC-1 implantation, mice received either NT (300 μg/kg or 600 μg/kg) or saline solution (control) subcutaneously three times a day for 6 days. Two groups of tumor-free mice received either saline or NT for 6 days. At sacrifice, jejunum and ileum were collected, weighed, and analysed for DNA and protein content. In the jejunum, NT combined with GLP-2 (from STC-1) increased weight, protein content (markers of mucosal hypertrophy), and DNA content (a marker of mucosal hyperplasia), compared to either NT or GLP-2 alone. In the ileum, the combination of NT and GLP-2 significantly increased weight and/or protein content compared to NT or GLP-2 alone. Administration of NT enhances the enterotrophic effects of GLP-2, augmenting hypertrophy of the entire small bowel and hyperplasia of the jejunum. The combination of NT and GLP-2 may be useful to enhance intestinal growth in patients with the short bowel syndrome.
KW - Glucagon-like peptide 2
KW - Intestinal growth factors
KW - Neurotensin
KW - Short bowel syndrome
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U2 - 10.1016/S1091-255X(99)80061-4
DO - 10.1016/S1091-255X(99)80061-4
M3 - Article
C2 - 10482697
AN - SCOPUS:0033155712
VL - 3
SP - 432
EP - 440
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
SN - 1091-255X
IS - 4
ER -