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Involvement of the cGMP pathway in mediating the insulin-inhibitory effect of melatonin in pancreatic beta-cells.

Authors: Stumpf, I  Muhlbauer, E  Peschke, E 
Citation: Stumpf I, etal., J Pineal Res. 2008 Oct;45(3):318-27. doi: 10.1111/j.1600-079X.2008.00593.x. Epub 2008 Mar 25.
Pubmed: (View Article at PubMed) PMID:18363673
DOI: Full-text: DOI:10.1111/j.1600-079X.2008.00593.x

Recent investigations have demonstrated an influence of melatonin on insulin secretion in pancreatic beta-cells. The effects are receptor-mediated via two parallel signaling pathways. The aim of this study was to examine the relevance of a second melatonin receptor (MT2) as well as the involvement of a third signaling cascade in mediating melatonin effects, i.e. the cyclic guanosine monophosphate (cGMP) pathway. Our results demonstrate that the insulin-inhibiting effect of melatonin could be partly reversed by preincubation with the unspecific melatonin receptor antagonist luzindole as well as by the MT2-receptor-specific antagonist 4P-PDOT (4-phenyl-2-propionamidotetraline). As melatonin is known to modulate cGMP concentration via the MT2 receptor, these data indicate transmission of the melatonin effects via the cGMP transduction cascade. Molecular investigations established the presence of different types of guanylate cyclases, cGMP-specific phosphodiesterases and cyclic nucleotide-gated channels in rat insulinoma beta-cells (INS1). Moreover, variations in mRNA expression were found when comparing day and night values as well as different states of glucose metabolism. Incubation experiments provided evidence that 3-isobutyl-1-methylxanthine (IBMX)-stimulated cGMP concentrations were significantly decreased in INS1 cells exposed to melatonin for 1 hr in a dose- and time-dependent manner. This effect could also be reversed by application of luzindole and 4P-PDOT. Stimulation with 8-Br-cGMP resulted in significantly increased insulin production. In conclusion, it could be demonstrated that the melatonin receptor subtype MT2 as well as the cGMP signaling pathway are involved in mediating the insulin-inhibiting effect of melatonin.

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CRRD Object Information
CRRD ID: 9588673
Created: 2014-11-04
Species: All species
Last Modified: 2014-11-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.