|Garcia, Rodrigo -|
|Afeche, Solange -|
|Scialfa, Julieta -|
|Amaral, Fernanda -|
|Santos, Sabrina -|
|Lima, Fabio -|
|Young, Martin -|
|Cipolla-Neto, Jose -|
Submitted to: Life Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 2, 2007
Publication Date: January 2, 2008
Citation: Garcia, R.A., Afeche, S.C., Scialfa, J.H., Amaral, F.G., Santos, S.H., Lima, F.B., Young, M.E., Cipolla-Neto, J. 2008. Insulin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland. Life Sciences. 82(1-2):108-114. Interpretive Summary: Melatonin is an important "time-of-day" signal in the body, which has many functions, including sleep control. Animals and humans generally eat only when they are awake. When we eat, our body produces insulin. We therefore hypothesized that insulin may influence the production of melatonin, to help synchronize time-of-day-dependent production and release into the blood. The results show that insulin increases the ability of the body to produce melatonin. These observations may help to explain the relationship between sleep, feeding, and time-of-day body functions.
Technical Abstract: 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.