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J Pineal Res. 2014 Aug;57(1):67-79. doi: 10.1111/jpi.12144. Epub 2014 Jun 3.

Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia.

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Laboratory of Neurobiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.


Melatonin is a neurohormone that works as a nighttime signal for circadian integrity and health maintenance. It is crucial for energy metabolism regulation, and the diabetes effects on its synthesis are unresolved. Using diverse techniques that included pineal microdialysis and ultrahigh-performance liquid chromatography, the present data show a clear acute and sustained melatonin synthesis reduction in diabetic rats as a result of pineal metabolism impairment that is unrelated to cell death. Hyperglycemia is the main cause of several diabetic complications, and its consequences in terms of melatonin production were assessed. Here, we show that local high glucose (HG) concentration is acutely detrimental to pineal melatonin synthesis in rats both in vivo and in vitro. The clinically depressive action of high blood glucose concentration in melatonin levels was also observed in type 1 diabetes patients who presented a negative correlation between hyperglycemia and 6-sulfatoxymelatonin excretion. Additionally, high-mean-glycemia type 1 diabetes patients presented lower 6-sulfatoxymelatonin levels when compared to control subjects. Although further studies are needed to fully clarify the mechanisms, the present results provide evidence that high circulating glucose levels interfere with pineal melatonin production. Given the essential role played by melatonin as a powerful antioxidant and in the control of energy homeostasis, sleep and biological rhythms and knowing that optimal glycemic control is usually an issue for patients with diabetes, melatonin supplementation may be considered as an additional tool to the current treatment.


K-ATPase; Na; arylalkylamine N-acetyltransferase; diabetes; hyperglycemia; melatonin; microdialysis; pineal

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