GLP-1 is a post-translational product of proglucagon produced in the distal intestinal tract and secreted during absorption of nutrients. GLP-1 is a potent insulin secretagogue and inhibits glucagon secretion. In addition, GLP-1 promotes gucose tolerance independent of its action on pancreatic hormones and has been suggested as a therapy for types I and II diabetes. The studies in this application will apply newly developed and highly specific radioimmunoassays to examine the secretory response of GLP-1 to nutrients in individuals across the spectrum of glucose tolerance. In addition, the site and mechanism of the extrapancreatic action of GLP-1 will be sought. Finally, the metabolism of GLP-1 in vivo and the potential bioactivity of other GLP-1-related peptides will be examined.