ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P654

Melatonin acts on pancreatic [beta]-cells via melatonin receptors using the cAMP-, IP3- and probably also the cGMP-signalling pathway

Ina Stumpf1, Eckhard Mühlbauer2 & Elmar Peschke1

1Martin-Luther-University Halle-Wittenberg, Halle, SA, Germany; 2Saxon Academy of Sciences, Leipzig, Sachsen, Germany.

Physiological and molecular examinations provided evidence for the receptor-mediated influence of the pineal hormone melatonin on insulin secretion of pancreatic β-cells. The predominant effect is a reduction the rate of insulin secretion transmitted by downregulation of intracellular cAMP concentrations. In addition, there is also evidence for an activation of the PLC-IP3-pathway. Further investigations established the existence of the melatonin-receptor MT1, and recently, also the MT2-receptor subtype could be detected in pancreatic β-cells.

The aim of this study was to examine the involvement of the MT2 melatonin receptor in the insulin-inhibiting effect and whether melatonin may mediate its effect via modulating the cGMP signal transduction pathway. Results of incubation experiments with rat insulinoma cells (INS1) demonstrate that melatonin inhibited the forskolin-stimulated insulin secretion. This effect could be reversed by pre-incubation with the unspecific melatonin receptor antagonist luzindole as well as by the MT2-receptor specific antagonist 4P-PDOT. Measurements of cGMP concentrations using an enzyme immunoassay showed that melatonin significantly inhibited total cGMP levels in a time-dependent manner. This effect could also be reversed by application of luzindole as well as 4P-PDOT, indicating that melatonin modulates cGMP concentrations via the MT2 receptor. Stimulation of INS1 cells with the membrane-permeable 8-Br-cGMP resulted in a dose- and time-dependent increase of insulin secretion. In conclusion, it could be demonstrated that the melatonin receptor subtype MT2 as well as the cGMP signalling pathway are involved in the insulin-inhibiting effect of melatonin. These data improve recent investigations about signal transduction- and receptor-mediated influences of melatonin on the pancreatic β-cells.

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