Enterotrophic effects of glucagon-like peptide 2 are enhanced by neurotensin.
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 x 10(6)) subcutaneously. Twenty-three days after STC-1 implantation, mice received either NT (300 microg/kg or 600 microg/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 analyzed 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.
Litvak
D A
DA
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77555-0533, USA.
Evers
B M
BM
Hellmich
M R
MR
Townsend
C M
CM
D000704:Analysis of Variance; D000818:Animals; D004247:DNA / Q000032:analysis; D004357:Drug Synergism; D005768:Gastrointestinal Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D005934:Glucagon / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D005935:Glucagonoma / Q000473:pathology; D006965:Hyperplasia; D006984:Hypertrophy; D007082:Ileum / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D007583:Jejunum / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009496:Neurotensin / Q000008:administration & dosage / Q000627:therapeutic use*; D009929:Organ Size; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011498:Protein Precursors / Q000008:administration & dosage / Q000627:therapeutic use*; D011506:Proteins / Q000032:analysis; D012778:Short Bowel Syndrome / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; D009496:Neurotensin; D004763:Glucagon-Like Peptides; D004247:DNA; D005934:Glucagon