INDUCTION OF INTESTINAL EPITHELIAL PROLIFERATION BY GLUCAGON-LIKE PEPTIDE-2

Injury, inflammation, or resection of the small intestine results in s evere compromise of intestinal function. Nevertheless, therapeutic str ategies for enhancing growth and repair of the intestinal mucosal epit helium are currently not available. We demonstrate that nude mice bear ing subcutaneous proglucagon-producing tumors exhibit marked prolifera tion of the small intestinal epithelium. The factor responsible for in ducing intestinal proliferation was identified as glucagon-like peptid e 2 (GLP-2), a 33-aa peptide with no previously ascribed biological fu nction. GLP-2 stimulated crypt cell proliferation and consistently ind uced a marked increase in bowel weight and villus growth of the jejunu m and ileum that was evident within 4 days after initiation of GLP-2 a dministration. These observations define a novel biological role for G LP-2 as an intestinal-derived peptide stimulator of small bowel epithe lial proliferation.