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Peschke, Elmar; Bach, Andreas G.; Mühlbauer, Eckhard

Parallel signaling pathways of melatonin in the pancreatic β‐cell

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  • Media type: E-Article
  • Title: Parallel signaling pathways of melatonin in the pancreatic β‐cell
  • Contributor: Peschke, Elmar; Bach, Andreas G.; Mühlbauer, Eckhard
  • imprint: Wiley, 2006
  • Published in: Journal of Pineal Research
  • Language: English
  • DOI: 10.1111/j.1600-079x.2005.00297.x
  • ISSN: 0742-3098; 1600-079X
  • Origination:
  • Footnote:
  • Description: <jats:p><jats:bold>Abstract: </jats:bold>Previous results demonstrated that melatonin inhibits cAMP production and stimulates IP<jats:sub>3</jats:sub>liberation in rat insulinoma INS1 cells, a model for the pancreatic<jats:italic>β</jats:italic>‐cell. This study addresses the impact of melatonin on insulin release. Insulin, cAMP and IP<jats:sub>3</jats:sub>levels of INS1 cells in a superfusion system were measured. Initially, forskolin was used to stimulate cAMP and subsequently insulin release. Incubation of forskolin (5 <jats:italic>μ</jats:italic>mol/L)‐stimulated cells with melatonin (100 nmol/L) inhibited cAMP and insulin levels (down to 60% of insulin and cAMP release). The G<jats:sub>i</jats:sub><jats:italic>α</jats:italic>‐protein‐inhibitor pertussis toxin (PTX) was used to distinguish between the G<jats:sub>i</jats:sub><jats:italic>α</jats:italic>‐dependent cAMP pathway and the G<jats:sub>i</jats:sub><jats:italic>α</jats:italic>‐independent IP<jats:sub>3</jats:sub>pathway. In our experiments we employed a specific stimulation pattern to prove proper inhibition of G<jats:sub>i</jats:sub><jats:italic>α</jats:italic>‐proteins by PTX. In INS1 cells incubated with 250 ng/mL PTX for 24 hr, melatonin was no longer able to inhibit the forskolin‐induced cAMP and insulin release. In a study, carbachol was used to stimulate IP<jats:sub>3</jats:sub>and subsequently insulin release. Surprisingly, incubation of carbachol (300 <jats:italic>μ</jats:italic>mol/L)‐stimulated cells with melatonin (100 nmol/L) inhibited insulin release (down to 75% of insulin release). Finally, in PTX‐incubated INS1 cells, melatonin (100 nmol/L) increased carbachol (300 <jats:italic>μ</jats:italic>mol/L)‐induced insulin release (up to 124% of insulin release). In conclusion, we found that the melatonin MT<jats:sub>1</jats:sub>‐receptor on pancreatic<jats:italic>β</jats:italic>‐cells is coupled to parallel signaling pathways, with opposite influences on insulin secretion. The cAMP‐ and subsequently insulin‐inhibiting signaling pathway involves PTX‐sensitive G<jats:sub>i</jats:sub><jats:italic>α</jats:italic>‐proteins and is predominant in terms of insulin release.</jats:p>