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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, 108 M), and
electrical nerve stimulation (NS) with or without 
-adrenergic blockade (phentolamine 105 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
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