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

Abstract

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.

Melatonin multiple effects on brown adipose tissue molecular machinery

“…Melatonin oral replacement reestablished Adrβ3 expression level, but did not prevent the phase delay. We suggest that this may be due to melatonin being available to PINX/Mel animals since the beginning of the dark phase, approximately 3 hours before the physiological rise observed in control animals, being that a limitation of the present study.…”

“…Melatonin has been shown to regulate BAT, acting as a recruiter and increasing its thermogenic capacity . Despite its regulatory role in other metabolic active tissues and the evidences of its interaction with BAT, little is known about its role in the metabolic thermogenic pathway either in its daily regulation or after acute challenges. The present work aimed to analyze that using pinealectomized and melatonin‐treated pinealectomized animals.…”

Global Fecal and Plasma Metabolic Dynamics Related to Helicobacter pylori Eradication

“…Recent experimental evidence suggested that melatonin may influence food intake, energy expenditure, the accumulation of energy in adipose tissue, insulin secretion and glycemic control (Peschke et al, 2006; Picinato et al, 2008; Prokopenko et al, 2009; Amaral et al, 2014b). It has been proposed that the reduction in melatonin production may induce insulin resistance, glucose intolerance, sleep disturbance, and metabolic circadian disorganization characterizing a state of chrono-disruption leading to metabolic disorders such as obesity (Pulimeno et al, 2013; Amaral et al, 2014a; Cipolla-Neto et al, 2014; Sharma et al, 2015).…”

Os efeitos do treinamento físico aeróbio sobre a síntese de melatonina pineal em ratos.

“…A glândula pineal é a responsável pela síntese e secreção do hormônio melatonina, que participa na organização temporal de ritmos biológicos atuando como mediadora entre o ciclo claro / escuro ambiental e os processos fisiológicos regulatórios incluindo a regulação endócrina da reprodução (GOLDMAN, 2001), na regulação do sistema cardiovascular, em particular da pressão arterial (MCKINLEY et al, 1990), na regulação de ciclos de atividaderepouso e vigília-sono (ARMSTRONG, 1989) e do sistema imunológico (FRASCHINI et al, 1990), além de desempenhar uma importante função fisiológica regulatória no metabolismo, influenciando inúmeros fatores ligados ao balanço energético (CIPOLLA-NETO et al, 2014).…”

“…Em animais diabeticos por STZ, a queda significativa na síntese de melatonina pineal, é causada pela hiperglicemia, pois ocorre a diminuição da expressão do receptor beta adrenérgico, do AMPc, no conteúdo da proteína e atividade da AANAT na pineal (AMARAL et al, 2014).…”