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.
N1 - Funding Information:
Deficiencies in intestinal regeneration and adaptation become clinically significant when the remaining functional intestine is unable to compensate completely for massive mucosal loss (e.g., massive intesti- From the Department of Surgery, The Universityo f Texas Medical Branch, Galveston, Tex. (Dr. Litvak is a visiting scientist from the University of California, Davis-East Bay, Oakland, Calif.). Supported in part by National Institutes of Health grants PO1 DK35608, RO1 DK48345, RO1 AG10885, and T32 DK07633. Presented in part at the Surgical Forum of the American College of Surgeons, Chicago, Ill., October 12-17, 1997; and at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17-20, 1998. Reprint requests: B. Mark Evers, M.D., Department of Surgery, The University of Texas Medical Branch, 301 University Blvd., Galveston, "IX 77555-0533.
PY - 1999
Y1 - 1999
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
UR - http://www.scopus.com/inward/record.url?scp=0033155712&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033155712&partnerID=8YFLogxK
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 -