Glucagon-like peptide-1 (GLP-1) (1-37) and the fraction derived from it, GLP-1 (7-36 amide), are peptides encoded by the preproglucagon gene and possibly co-secreted with enteroglucagon. When added at a 25-nM concentration, GLP-1 (7-36 amide) decreased the release of glucagon from the perfused rat pancreas from 68.5 +/- 9.0 pg/ml to 41.5 +/- 11.5 pg/ml at 2 min in the presence of 11.2 mM glucose (P less than 0.01), and from 196.0 +/- 32.5 pg/ml to 87.0 +/- 23.5 pg/ml at 5 min in the presence of 2.8 mM glucose (P less than 0.05). Insulin levels increased from 12.6 +/- 3.0 microU/ml to 48.9 +/- 14.0 microU/ml at 10 min in the presence of 11.2 mM glucose (P less than 0.05) and from 2.0 +/- 0.4 microU/ml to 8.2 +/- 2.3 microU/ml at 2 min in the presence of 2.8 mM glucose (P less than 0.05). Glucagon and insulin release were not affected significantly by GLP-1 (1-37), irrespective of glucose concentration. We suggest that GLP-1 (7-36 amide) rather than enteroglucagon may be the true physiologic gut hormone and that it may act as 'incretin' in the enteroinsular axis. We suggest further that the glucagonostatic and insulinotropic activities of this peptide are unique and might be important in islet-cell function.