Journal
HORMONE AND METABOLIC RESEARCH
Volume 41, Issue 11, Pages 805-813Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0029-1225631
Keywords
calcium/calmodulin-dependent kinase IV; calcium/calmodulin-dependent kinase 2d; pancreatic islet; insulin secretion
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Funding
- Wilhelm-Roux-Anschubforderung [FKZ 15/13]
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The objective of the present study was to examine the effects of melatonin on transcripts of isoforms of calcium/calmodulin-dependent protein kinases in rat insulinoma P-cells INS-1. Investigations show that calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d are expressed in human and rat pancreatic islets and INS-1 cells. By application of either forskolin or 3-isobutyl-1-methylxanthine for 6 hours, calcium spiking was evoked and the release of insulin was increased. The expression of the calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d transcripts was significantly increased due to forskolin or 3-isobutyl-1-methylxanthine. Acute melatonin treatment (6h) in the presence of either forskolin or 3-isobutyl-1-methyl-xanthine caused a significant decrease in insulin release and induced significant downregulation of calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d transcripts in INS-1 batch cultures. The attenuating effect of melatonin on transcripts could be almost completely reversed by preincubation with the melatonin receptor antagonist luzindole. Thus, the insulin-inhibiting effect of melatonin in INS-1 cells is associated with significant changes in transcripts of calcium-signaling components suggesting that melatonin influences gene expression of components, which are known to be involved in insulin secretion or insulin gene expression.
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