Effects Of Melatonin And Estrogen On Insulin Secretion In Vitro

Melatonin is a steroid hormone secreted by the hypothalamic pineal gland,which plays an important role in circadian rhythm,immune system,endocrine system,reproductive and cardiovascular systems.The function of melatonin is mainly mediated by two melatonin receptors(MTNR1A and MTNR1B)located on the cell membrane.The MTNR1B gene mutation is closely related to the function of islet ? cells,and the MTNR1B gene mutation increases the risk of type 2 diabetes(T2DM)and gestational diabetes(GDM).During our previous clinical investigation,it was found that the single nucleotide polymorphism of the MTNR1B gene in pregnant women in the southwestern region significantly affected insulin release levels and blood glucose concentrations during pregnancy.Because the mechanism of action of melatonin on blood glucose during pregnancy is still unclear,this study was based on the construction of MTNR1B mutant and the choice of estrogen to simulate the pregnancy environment,to observe the effect of melatonin on insulin secretion.The effect of melatonin and estrogen on insulin release provides new ideas and directions for the diagnosis and treatment of gestational diabetes.Methods:(1)Based on the analysis of MTNR1B exon sequence and pregnancy glucose metabolism in more than 2000 pregnant women collected in the southwest region,the research team screened and constructed three MTNR1B mutants related to pregnancy glucose metabolism.They are 71G>A(G24E),589A>G(S197G),974C>T(A325V).In this experiment,the function of the mutant and the expression of the target protein were detected in cell model.(2)The pregnancy environment was simulated by different concentrations of estrogen,and insulin release was observed in mouse islet cell line,mouse primary cells and human islet cells by melatonin interference.Results:In this study,the functional status of three newly constructed MTNR1B mutant expression vectors was examined.The changes of insulin with glucose concentration in islet cell lines and primary cells were determined.Low concentration of estriol significantly inhibited the release of insulin and the difference was statistically significant.In primary human islet cells,melatonin inhibited the secretion of insulin and the difference was statistically significant.After the addition of low concentration of estriol,the inhibiting effect was partially reversed.On the basis of inhibiting insulin release by melatonin,the degree of inhibiting insulin release by melatonin was deepened after high-concentration estriol treatment.Conclusion:Melatonin inhibited insulin release of islet cells,low concentration estriol inhibited insulin release of islet cells.A significant increase in estriol during pregnancy affects melatonin and melatonin receptor-mediated signaling pathways regulating insulin release.