title: Melatonin influences somatostatin secretion from human pancreatic δ-cells via MT1 and MT2 receptors.
abstract: Melatonin is an effector of the diurnal clock on pancreatic islets. The membrane receptor-transmitted inhibitory influence of melatonin on insulin secretion is well established and contrasts with the reported stimulation of glucagon release from α-cells. Virtually, nothing is known concerning the melatonin-mediated effects on islet δ-cells. Analysis of a human pancreatic δ-cell model, the cell line QGP-1, and the use of a somatostatin-specific radioimmunoassay showed that melatonin primarily has an inhibitory effect on somatostatin secretion in the physiological concentration range. In the pharmacological range, melatonin elicited slightly increased somatostatin release from δ-cells. Cyclic adenosine monophosphate (cAMP) is the major second messenger dose-dependently stimulating somatostatin secretion, in experiments employing the membrane-permeable 8-Br-cAMP. 8-Br-cyclic guanosine monophosphate proved to be of only minor relevance to somatostatin release. As the inhibitory effect of 1 nm melatonin was reversed after incubation of QGP-1 cells with the nonselective melatonin receptor antagonist luzindole, but not with the MT2-selective antagonist 4-P-PDOT (4-phenyl-2-propionamidotetraline), an involvement of the MT1 receptor can be assumed. Somatostatin release from the δ-cells at low glucose concentrations was significantly inhibited during co-incubation with 1 nm melatonin, an effect which was less pronounced at higher glucose levels. Transient expression experiments, overexpressing MT1, MT2, or a deletion variant as a control, indicated that the MT1 and not the MT2 receptor was the major transmitter of the inhibitory melatonin effect. These data point to a significant influence of melatonin on pancreatic δ-cells and on somatostatin release.
authors.affiliation: Institute of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Zibolka
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mühlbauer
authors.forename: Elmar
authors.initials: E
authors.lastname: Peschke
mesh_terms: D002460:Cell Line; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008550:Melatonin / Q000494:pharmacology*; D011863:Radioimmunoassay; D044122:Receptor, Melatonin, MT1 / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*
chemical_list: D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D013004:Somatostatin; D008550:Melatonin
keywords: QGP-1; melatonin receptors MT1 and MT2; pancreatic δ-cell; second messenger; somatostatin