Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 288; no. 3; p. G431
• Main Authors: Martin, G R, Wallace, L E, Hartmann, B, Holst, J J, Demchyshyn, L, Toney, K, Sigalet, D L
• Format: Journal Article
• Language: English
• Published: United States 01-03-2005
• Subjects: Adaptation, Physiological; Animals; Antimetabolites; Body Weight - physiology; Bromodeoxyuridine; Cell Proliferation; Dietary Fats - metabolism; Dietary Proteins - metabolism; Enzyme-Linked Immunosorbent Assay; Food; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Intestinal Absorption - physiology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestines - pathology; Intestines - physiopathology; Male; Peptides - blood; Peptides - metabolism; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome - pathology; Short Bowel Syndrome - physiopathology
• DOI: 10.1152/ajpgi.00242.2004
• ISSN: 0193-1857

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.