Melatonin influences somatostatin secretion in the human pancreatic δ-cell line QGP-1

Objectives: Disruption of circadian processes in pancreatic islets can lead to metabolic diseases like diabetes mellitus type 2. Previous research has focused on the inhibitory influence of melatonin on the release of insulin and on its stimulatory role in glucagon secretion, both mediated through activation of the membrane melatonin receptors MT1 and/or MT2. Until now no information was available concerning the influence of melatonin on somatostatin secretion from pancreatic δ-cells.

Methods: Employing the human somatostatinoma cell line QGP-1 somatostatin and second messengers cAMP and cGMP were measured after incubation with increasing doses of melatonin or after co-incubation with melatonin receptor antagonists through a specific radioimmunoassay and an enzyme immunoassay. Both melatonin receptors were identified by real-time RT-PCR and immunocytochemistry. To study melatonin receptor-mediated effects, QGP-1 cells overexpressing MT1 or MT2 were incubated with melatonin in transient transfection experiments. For statistical analyses the Mann-Whitney U-test was used.

Results: Melatonin exerted an inhibitory effect on somatostatin secretion in the physiological range, indicated by a decrease in cAMP and cGMP concentrations. Since the inhibitory effect was reversed after incubation with the non-selective melatonin receptor antagonist luzindole, but not with the MT2-selective antagonist 4-P-PDOT, an involvement of the MT1 receptor can be assumed. This was corroborated in the transfection experiments, where MT1 proved to be the major transmitter of the inhibitory melatonin effect.

Conclusions: These data indicate the significant influences melatonin has on pancreatic somatostatin secretion and may enhance our understanding of the role melatonin plays in modulating paracrine secretory processes in pancreatic islets.