Glucagon-like peptide-1(7-36NH2) is a potent stimulator of insulin secretion, as well as of somatostatin-14 (SS-14) release from the pancreatic and gastric D-cells. To investigate the possible effects of this peptide on release of intestinal somatostatin (SS-28 and SS-14, rat intestinal cultures were treated with 10(-12)-10(-6) M GLP-1(7-36NH2), as well as with the structurally related peptides, GLP-1(1-36NH2) and GLP-2. Both forms of GLP-1 stimulated does-dependent increases in intestinal somatostatin; secretion reached 643 +/- 126% of controls (p < 0.001) after treatment with 10(-6) M GLP-1(7-36NH2), and 398 +/-76% of controls (p < 0.001) after 10(-6) M GLP-1(1-36NH2). Thus, GLP-1(7-36NH2) was more effective than GLP-1(1-36NH2) in stimulating secretion of intestinal somatostatin-like immunoreactivity (SLI) (p < 0.05). GLP-2 did not affect intestinal somatostatin release. Gel permeation analysis demonstrated that 10(-6) M GLP-1(7-36NH2) stimulated SS-28 by 2.9 +/- 0.4-fold and SS-14 by 9.1 +/- 3.7-fold, whereas GLP-1(1-36NH2) exerted equivalent effects (2.8 +/- 0.9-fold) on both forms of somatostatin. These findings define a novel biological role for GLP-1(7-36NH2) in the regulation of intestinal somatostatin secretion, and demonstrate that GLP-1(1-36NH2) exerts unique biological activities in this system.