Hormonal therapy for short bowel syndrome.
OBJECTIVE
Treatment of short bowel syndrome (SBS) can be difficult; this study examines the effect of parental administration of different peptide hormones in a rat model of SBS.


METHODS
Juvenile male Lewis rats (220 to 240 g) underwent resection of the proximal 90% of small bowel and were assigned randomly to treatment groups: growth hormone (GH), insulinlike growth factor-1 (IGF-1), glucagonlike peptide-2 (GLP-2; given as ALX-0600, a potent protease resistant analogue of the human GLP-2), control-resected (Con-R), or control-transected (Con-T). Drugs were delivered by continuous subcutaneous infusion via Alzet mini-pumps: controls received equivalent volumes of drug vehicle. Animals were pair-fed (23 g chow per day) and followed up for 14 days monitoring weight gain. Animals were killed and active transport, hormone profiles, and intestinal morphology were assessed.


RESULTS
Hormonal treatments significantly increased weight gain in all groups (GH, 9.9+/-4.9; IGF-1, 6.0+/-9.6; and GLP-2, 0.8+/-2.7 v. -6.2+/-4.7 in untreated resected animals [weight as percentile initial weight]). This was associated with a significant alteration in intestinal morphology in the IGF-1-treated animals, and an increase in glucose transport rates in all hormonally treated animals when compared with untreated control resected animals.


CONCLUSIONS
These results show that IGF-1, GH, and GLP-2 all improve short-term weight gain after massive bowel resection in a rat model. The effects seen on weight gain may be caused by improved dietary nutrient absorption from an increase in the intestinal surface area or increase in transporting activity or alterations in the metabolic efficiency of the animal. These findings suggest further studies of these therapies as treatment for short-bowel syndrome are indicated.
Sigalet
D L
DL
Department of Surgery, The Alberta Children's Hospital, Calgary, Canada.
Martin
G R
GR
D000818:Animals; D005069:Evaluation Studies as Topic; D005768:Gastrointestinal Hormones / Q000627:therapeutic use; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006133:Growth Substances / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D007408:Intestinal Absorption; D008297:Male; D009929:Organ Size; D010455:Peptides / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D006133:Growth Substances; D010455:Peptides; D004763:Glucagon-Like Peptides; D007334:Insulin-Like Growth Factor I