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Parallel signaling pathways of melatonin in the pancreatic β‐cell
Author(s) -
Peschke Elmar,
Bach Andreas G.,
Mühlbauer Eckhard
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2005.00297.x
Subject(s) - forskolin , melatonin , insulin , medicine , endocrinology , carbachol , pertussis toxin , biology , melatonin receptor , chemistry , stimulation , g protein , receptor
Previous results demonstrated that melatonin inhibits cAMP production and stimulates IP 3 liberation in rat insulinoma INS1 cells, a model for the pancreatic β ‐cell. This study addresses the impact of melatonin on insulin release. Insulin, cAMP and IP 3 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 μ mol/L)‐stimulated cells with melatonin (100 nmol/L) inhibited cAMP and insulin levels (down to 60% of insulin and cAMP release). The G i α ‐protein‐inhibitor pertussis toxin (PTX) was used to distinguish between the G i α ‐dependent cAMP pathway and the G i α ‐independent IP 3 pathway. In our experiments we employed a specific stimulation pattern to prove proper inhibition of G i α ‐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 3 and subsequently insulin release. Surprisingly, incubation of carbachol (300 μ 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 μ mol/L)‐induced insulin release (up to 124% of insulin release). In conclusion, we found that the melatonin MT 1 ‐receptor on pancreatic β ‐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 i α ‐proteins and is predominant in terms of insulin release.