Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops.

The structure-activity relationship of sugars inducing secretion of glucagon-like peptide-1 from the gut was examined using intestinal loops prepared from the terminal portion of the ileum of dogs. The plasma glucagon-like peptide-1 concentration in a mesenteric vein draining only the looped region of the intestine was increased after infusion of 139 mmol/l solutions of D-glucose, D-galactose, D-glucuronic acid, 3-0-methyl-D-glucose, maltose, sucrose or maltitol into the intestinal lumen, but not after infusion of solutions of D-fructose, D-fucose, D-mannose, D-xylose or lactose. The increases in plasma glucagon-like peptide-1 concentration correlated with the corresponding increases in glucagon-like immunoreactivity induced by these sugars. The plasma glucose level of the regional mesenteric vein increased significantly from the basal level after instillation of D-glucose, but not after instillation of other sugars. It is suggested that cells of the gut have a glucose sensor for release of products of the glucagon gene and that this sensor has specific steric requirements. The sugars that induced glucagon-like peptide-1 release share the molecular features of electron density near C(6), an equatorial hydroxyl at C(2), and an axial hydroxyl at C(1), which could account for their recognition by the glucose sensor to initiate the releases of glucagon-like peptide-1 and glucagon-like immunoreactivity.