Leptin and melatonin play an important role in the regulation of body mass and energy balance. Both hormones show a circadian rhythm, with increasing values at night. In addition, melatonin receptors were recently described in adipocytes, where leptin is synthesized. Here, we investigated the influence of melatonin and its interaction with insulin and dexamethasone on leptin expression. Isolated rat adipocytes were incubated with melatonin (1 nM) alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) for 6 h. Melatonin or insulin alone did not affect leptin expression, but together they increased it by 120%. Dexamethasone increased leptin mRNA content (105%), and this effect was not enhanced by melatonin. Simultaneous treatment with the three hormones provoked a further increase in leptin release (250%) and leptin mRNA (100%). Melatonin prevented the forskolin-induced inhibition (95%) of leptin expression. In addition, melatonin's ability to stimulate leptin release (in the presence of insulin) was completely blocked by pertussis toxin and luzindole. To gain further insight into the molecular basis of melatonin and insulin synergism, the insulin-signaling pathway was investigated. Melatonin increased the insulin-induced insulin receptor-beta tyrosine phosphorylation, which led to an increased serine phosphorylation of the downstream convergent protein Akt. We concluded that melatonin interacts with insulin and upregulates insulin-stimulated leptin expression. These effects are caused by melatonin binding to the pertussis toxin-sensitive G(i) protein-coupled membrane receptor (MT1 subtype) and the cross talk with insulin, since insulin receptor and its convergent target Akt are coactivated by melatonin.

The primary hormone of the vertebrate pineal gland, melatonin, has been identified broadly throughout the tree of life, in animals, plants, and fungi, supporting a deep evolutionary origin for this signaling molecule. However, some key groups have not been studied. Echinoderms, deuterostome animals, are one of these groups. Herein we study the presence of melatonin and enzymes of its pathway in the sea star Echinaster brasiliensis. We demonstrate that E. brasiliensis produces endogenous melatonin, in the gonads, under a circadian pattern with a nocturnal peak of production. We also show that the enzymes arylalkylamine N-acetyltransferase (AANAT) and tryptophan hydroxylase (TPH) are present and are probably regulating the melatonin production.

A influência da glândula pineal sobre o metabolismo de carboidratos vem sendo investigada há décadas. Entretanto, resultados contraditórios não esclarecem, até o momento, o verdadeiro papel da melatonina sobre a homeostasia dos carboidratos. Através de estudos recentes, contribuímos de maneira ineqüívoca para a caracterização do papel da glândula pineal como moduladora do metabolismo de carboidratos. Além disso, à luz dos conhecimentos atuais, demonstramos quais passos do mecanismo de ação da insulina estão envolvidos nessa modulação. Nossos estudos revelaram que a pinealectomia promove um quadro de resistência à insulina, sem obesidade. A captação máxima de 2-deoxi-glicose, estimulada por insulina, em adipócitos isolados está diminuída, sem entretanto modificar a capacidade da insulina ligar-se ao seu receptor e estimular a fosforilação dos substratos intracelulares representados pela pp 185. Por outro lado, em vários tecidos sensíveis à insulina, observou-se uma diminuição no conteúdo da proteína transportadora de glicose GLUT4, mas diminuição no mRNA do GLUT4 apenas em alguns desses tecidos, sugerindo uma regulação tecido-específica. Adicionalmente, foi demonstrado que a regulação da glândula pineal sobre o metabolismo de carboidratos é mediado pela melatonina: o hormônio aumentou a sensibilidade à insulina de adipócitos isolados e o tratamento de reposição com melatonina restaurou o conteúdo de GLUT4 no tecido adiposo branco. Em síntese, os estudos aqui relatados evidenciam um importante papel da glândula pineal na modulação da homeostasia de carboidratos. Essa regulação é dependente da melatonina e pode ser resumida, até o presente momento, como um aumento da sensibilidade tecidual à insulina, que envolve alterações na expressão gênica do GLUT4.
For decades, the influence of the pineal gland on carbohydrate metabolism has been investigated. However, contradictory results have not yet elucidated the role played by melatonin in carbohydrate homeostasis. In our recent studies, we have contributed to characterize the role of the pineal gland as a modulator of carbohydrate metabolism. In addition, based on present-day knowledge, we have demonstrated the steps of insulin action mechanism involved in this modulation. Our studies reveal that pinealectomy causes a condition of obesity-free insulin resistance. The maximum uptake of 2-deoxi-glucose prompted by insulin in isolated adipocytes is diminished, without however changing the insulin capacity to bind to its receptor, and to stimulate the phosphorilation of intracellular substrates represented by pp 185. Conversely, in several insulin-sensitive tissues, our studies detected a decrease in the amount of glucose transporter protein GLUT4, and a decrease in GLUT4 mRNA in only some of these tissues, suggesting a tissue-specific regulation. Additionally, it was demonstrated that the pineal gland regulation influences carbohydrate metabolism through melatonin, by our demonstration that the hormone increased insulin sensitivity of isolated adipocytes, and that melato...

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Resumo-Neste artigo, é introduzido um novo método para o cálculo de uma transformada discreta de Fourier fracionária (DFrFT) com complexidade aritmética reduzida, quando comparado com a complexidade O(N 2 ) do cálculo direto. A abordagem proposta explora propriedades de uma autobase Hermite-Gaussiana da transformada discreta de Fourier recentemente introduzida na literatura, que é usada para definir a DFrFT; o método requer menos da metade do número de adições requerido por outros métodos do estado-da-arte e, quando utilizado na representação compacta de sinais no domínio fracionário, mais de 45% das multiplicações e 75% das adições são economizadas, em comparação a esses mesmos algoritmos.Palavras-Chave-Transformada discreta de Fourier fracionária, autovetores Hermite-Gaussianos, algoritmos rápidos, complexidade aritmética.Abstract-In this paper, we introduce a method for computing a discrete fractional Fourier transform (DFrFT) with reduced arithmetic complexity, when compared to the O(N 2 ) complexity of the corresponding direct computation. Our approach exploits properties of a recently introduced closed-form Hermite-Gaussian-like discrete Fourier transform eigenbasis, which is used to define the DFrFT; it requires less than half the number of additions demanded by other state-of-the-art methods and, when applied to compact representation of signals in the fractional domain, more then 45% of the multiplications and 75% of the additions are saved, when compared with the same algorithms.