Transcripts of calcium/calmodulin-dependent kinases are changed after forskolin- or IBMX-induced insulin secretion due to melatonin treatment of rat insulinoma beta-cells (INS-1).
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 beta-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 (6 h) in the presence of either forskolin or 3-isobutyl-1-methylxanthine 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.
Bazwinsky-Wutschke
I
I
Institute of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle, Germany. ivonne.bazwinsky@medizin.uni-halle.de
Mühlbauer
E
E
Wolgast
S
S
Peschke
E
E
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007340:Insulinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005576:Colforsin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D008550:Melatonin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine