GLP-2 augments the adaptive response to massive intestinal resection in rat

Abstract

To determine whether treatment with a potent protease-resistant analog of human glucagon-like peptide 2 (GLP-2) might augment the adaptive response to massive intestinal resection, rats were divided into resected, which had 75% of the midjejunoileum removed, sham-resected, and nonsurgical groups. Within each group, animals were assigned to 21 days of treatment with the drug (0.1 μg/g of the GLP-2 analog in phosphate-buffered saline) or vehicle alone subcutaneously twice daily. Food intake; weight gain; jejunal and ileal diameters, total and mucosal wet weights per centimeter, crypt depths, and villus heights; mucosal sucrase activity, milligrams of protein per centimeter, and micrograms of DNA per centimeter; andd-xylose absorption were measured. There was a significant increase in diameter, total and mucosal wet weights per centimeter, crypt-villus height, sucrase activity, milligrams of protein per centimeter and micrograms of DNA per centimeter in both the jejunum and ileum in response to resection and a significant additive response to the GLP-2 analog in the jejunum but not in the ileum. The ratio of milligrams of protein per centimeter to micrograms of DNA per centimeter of mucosa was not different among groups, consistent with hyperplasia.d-Xylose absorption was significantly reduced in response to resection; however, the GLP-2 analog enhanced the absorptive capacity in control animals and restored the absorptive capacity in resected animals. Thus the GLP-2 analog induces mucosal hyperplasia and enhances the rate and magnitude of the proximal intestinal adaptive response to massive resection.

International Union of Pharmacology. XXXV. The Glucagon Receptor Family

“…GLP-2 administration to rodents enhances villus growth and increases small bowel mass, with weaker but detectable trophic effects observed in the large bowel and stomach (Drucker et al, 1997a,b;Tsai et al, 1997a,b). GLP-2 also rapidly up-regulates hexose transport and nutrient absorption (Cheeseman and Tsang, 1996;Brubaker et al, 1997) and enhances sugar absorption and intestinal adaptation in rats following major small bowel resection (Scott et al, 1998). GLP-2 reduces intestinal permeability in rodents within hours of peptide administration in vivo but has no effect on mucosal permeability when administered in vitro (Benjamin et al, 2000), consistent with the established indirect actions of GLP-2 (Drucker, 2001b).…”

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

“…10 Furthermore, treatment with GLP-2 improves absorptive capacity in rats with massive resection of the small intestine. 11 In addition to these intestinotrophic effects, GLP-2 has inhibitory effects on gastrointestinal motility 12 and secretion, 13 and it has been speculated that GLP-2 augments the effects of the 2 other ileal-brake hormones, GLP-1 and peptide YY. Therefore, GLP-2 has received much attention as a potential therapeutic agent in the treatment of patients with short-bowel syndrome.…”

Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

“…GLP-2 is uniquely trophic for the intestine (8). It can stimulate residual small-intestinal adaptation by increasing crypt cell proliferation and inhibiting apoptosis, thereby increasing villus height, crypt depth, mucosal mass, and overall small-intestinal length and weight (9)(10)(11). Functionally, GLP-2 increases activities of mucosal enzymes and therefore increases digestion and absorption (12).…”