Garcia Rodrigo Antonio Peliciari, Afeche Solange Castro, Scialfa Julieta Helena, do Amaral Fernanda Gaspar, dos Santos Sabrina Heloísa José, Lima Fabio Bessa, Young Martin Elliot, Cipolla-Neto José
University of São Paulo, Institute of Biomedical Sciences, Department of Physiology and Biophysics, Av. Prof. Lineu Prestes 1524, 1st floor, room 118, Sao Paulo, SP, CEP 05508-900, Brazil.
Life Sci. 2008 Jan 2;82(1-2):108-14. doi: 10.1016/j.lfs.2007.10.016. Epub 2007 Nov 1.
The mammalian pineal gland synthesizes melatonin in a circadian manner, peaking during the dark phase. This synthesis is primarily regulated by sympathetic innervations via noradrenergic fibers, but is also modulated by many peptidergic and hormonal systems. A growing number of studies reveal a complex role for melatonin in influencing various physiological processes, including modulation of insulin secretion and action. In contrast, a role for insulin as a modulator of melatonin synthesis has not been investigated previously. The aim of the current study was to determine whether insulin modulates norepinephrine (NE)-mediated melatonin synthesis. The results demonstrate that insulin (10(- 8)M) potentiated norepinephrine-mediated melatonin synthesis and tryptophan hydroxylase (TPOH) activity in ex vivo incubated pineal glands. When ex vivo incubated pineal glands were synchronized (12h NE-stimulation, followed by 12h incubation in the absence of NE), insulin potentiated NE-mediated melatonin synthesis and arylalkylamine-N-acetyltransferase (AANAT) activity. Insulin did not affect the activity of hydroxyindole-O-methyltranferase (HIOMT), nor the gene expression of tpoh, aanat, or hiomt, under any of the conditions investigated. We conclude that insulin potentiates NE-mediated melatonin synthesis in cultured rat pineal gland, potentially through post-transcriptional events.
哺乳动物的松果体以昼夜节律的方式合成褪黑素，在黑暗阶段达到峰值。这种合成主要受去甲肾上腺素能纤维的交感神经支配调节，但也受到许多肽能和激素系统的调节。越来越多的研究揭示了褪黑素在影响各种生理过程中的复杂作用，包括调节胰岛素分泌和作用。相比之下，胰岛素作为褪黑素合成调节因子的作用此前尚未得到研究。本研究的目的是确定胰岛素是否调节去甲肾上腺素（NE）介导的褪黑素合成。结果表明，胰岛素（10(-8)M）增强了体外孵育的松果体中去甲肾上腺素介导的褪黑素合成和色氨酸羟化酶（TPOH）活性。当体外孵育的松果体同步化（12小时NE刺激，然后在无NE的情况下孵育12小时）时，胰岛素增强了NE介导的褪黑素合成和芳基烷基胺-N-乙酰基转移酶（AANAT）活性。在所研究的任何条件下，胰岛素均未影响羟基吲哚-O-甲基转移酶（HIOMT）的活性，也未影响tpoh、aanat或hiomt的基因表达。我们得出结论，胰岛素可能通过转录后事件增强培养的大鼠松果体中NE介导的褪黑素合成。
