Somatostatin restrains the secretion of glucagon-like peptide-1 and -2 from isolated perfused porcine ileum

1 Department of Medical Physiology, the Panum Institute, University of Copenhagen, DK-2200 Copenhagen; and 2 Novo-Nordisk, DK-2880 Bagsværd, Denmark Suspecting that paracrine inhibition might influence neuronal regulation of the endocrine L cells, we studied the role of somatostatin (SS) in the regulation of the secretion of the proglucagon-derived hormones glucagon-like peptide-1 and -2 (GLP-1 and GLP-2). This was examined using the isolated perfused porcine ileum stimulated with acetylcholine (ACh, 10 6 M), neuromedin C (NC, 10 8 M), and electrical nerve stimulation (NS) with or without -adrenergic blockade (phentolamine 10 5 M), and perfusion with a high-affinity monoclonal antibody against SS. ACh and NC significantly increased GLP secretion, whereas NS had little effect. SS immunoneutralization increased GLP secretion eight- to ninefold but had little influence on the GLP responses to ACh, NC, and NS. Basal SS secretion (mainly SS28) was unaffected by NS alone. Phentolamine + NS and NC abstract strongly stimulated release mainly of SS14, whereas ACh had little effect. Infused intravascularly, SS14 weakly and SS28 strongly inhibited GLP secretion. We conclude that GLP secretion is tonically inhibited by a local release of SS28 from epithelial paracrine cells, whereas SS14, supposedly derived from enteric neurons, only weakly influences GLP secretion. paracrine activity; L cells; bombesin; enteric nervous system; gastrointestinal hormones; immunoneutralization