Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome.
Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals (P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection (r(2) = 0.71; P < 0.001), CCP (r(2) = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.
Martin
G R
GR
University of Calgary, Gastrointestinal Research Group, Health Sciences Bldg, Rm. 1746, 3330 Hospital Dr. NW, Calgary, AB, Canada T2N 4N1. marting@ucalgary.ca
Wallace
L E
LE
Hartmann
B
B
Holst
J J
JJ
Demchyshyn
L
L
Toney
K
K
Sigalet
D L
DL
D000222:Adaptation, Physiological; D000818:Animals; D000963:Antimetabolites; D001835:Body Weight / Q000502:physiology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D004041:Dietary Fats / Q000378:metabolism; D004044:Dietary Proteins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005502:Food; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000473:pathology* / Q000503:physiopathology*
D000963:Antimetabolites; D004041:Dietary Fats; D004044:Dietary Proteins; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides; D001973:Bromodeoxyuridine