PMID:16441556

Citation	Peschke, E, Bach, AG and Mühlbauer, E (2006) Parallel signaling pathways of melatonin in the pancreatic beta-cell. J. Pineal Res. 40:184-91
Abstract	Previous results demonstrated that melatonin inhibits cAMP production and stimulates IP(3) liberation in rat insulinoma INS1 cells, a model for the pancreatic beta-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 micromol/L)-stimulated cells with melatonin (100 nmol/L) inhibited cAMP and insulin levels (down to 60% of insulin and cAMP release). The G(i)alpha-protein-inhibitor pertussis toxin (PTX) was used to distinguish between the G(i)alpha-dependent cAMP pathway and the G(i)alpha-independent IP(3) pathway. In our experiments we employed a specific stimulation pattern to prove proper inhibition of G(i)alpha-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 micromol/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 micromol/L)-induced insulin release (up to 124% of insulin release). In conclusion, we found that the melatonin MT(1)-receptor on pancreatic beta-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)alpha-proteins and is predominant in terms of insulin release.
Links	PubMed Online version:10.1111/j.1600-079X.2005.00297.x
Keywords	Animals; Cell Line, Tumor; Cyclic AMP/metabolism; Heterotrimeric GTP-Binding Proteins/metabolism; Inositol 1,4,5-Trisphosphate/metabolism; Insulin/metabolism; Insulin-Secreting Cells/physiology; Melatonin/physiology; Pertussis Toxin; Rats; Second Messenger Systems/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status

References

See Help:References for how to manage references in GONUTS.