Impairment of retinal melatonin synthesis in diabetic Wistar rat.

A síntese de melatonina na retina ocorre de maneira circadiana na camada fotorreceptora, e age localmente promovendo a adaptação fisiológica da retina ao escoto-período. Sabendo-se que o estresse oxidativo contribui com o desenvolvimento da retinopatia diabética e que a melatonina é um poderoso antioxidante natural, o objetivo deste trabalho foi avaliar na retina de animais diabéticos o conteúdo de melatonina e as enzimas envolvidas em sua via de síntese. Ratos Wistar (250-280g, 12h/12h claro/escuro) tiveram o quadro diabético induzido por STZ e foram tratados ou não com insulina. Os animais foram sacrificados 3 dias pós-indução. Os resultados mostraram que o diabetes causa a diminuição no conteúdo de melatonina retiniana devido à redução da atividade da AANAT causada pela queda no conteúdo de AMPc. O tratamento com insulina restabeleceu tanto o perfil de atividade da AANAT quanto à síntese de melatonina. Supõe-se que as retinas dos animais diabéticos estão mais vulneráveis aos danos decorrentes do quadro diabético, já que a síntese da melatonina está diminuída.Melatonin controls several retinal physiologic rhythmic phenomena besides being the most powerful natural free radical scavenger. The aim of this work is evaluating the retinal melatonin diurnal profile of diabetic rats. Male Wistar rats were diabetic-induced by an injection of STZ and some of them were treated with insulin (6U/day). Retinas were obtained throughout the 24h light-dark cycle for retinal melatonin content, enzymes activity, cAMP content and gene expression analysis. Control animals showed a retinal melatonin daily rhythm with high levels at night while diabetic rats presented a reduction. The AANAT activity showed a daily rhythm with high levels at night in the control group. This daily fluctuation was vanished in STZ-induced diabetic rats and insulin-treatment restored both parameters. We suppose the AANAT activity reduction observed is due to the reduced cAMP content. As melatonin plays an important role modulating circadian functions, this impairment could compromise the retinal physiological homeostasis

Impairment of retinal melatonin synthesis in diabetic Wistar rat.

A síntese de melatonina na retina ocorre de maneira circadiana na camada fotorreceptora, e age localmente promovendo a adaptação fisiológica da retina ao escoto-período. Sabendo-se que o estresse oxidativo contribui com o desenvolvimento da retinopatia diabética e que a melatonina é um poderoso antioxidante natural, o objetivo deste trabalho foi avaliar na retina de animais diabéticos o conteúdo de melatonina e as enzimas envolvidas em sua via de síntese. Ratos Wistar (250-280g, 12h/12h claro/escuro) tiveram o quadro diabético induzido por STZ e foram tratados ou não com insulina. Os animais foram sacrificados 3 dias pós-indução. Os resultados mostraram que o diabetes causa a diminuição no conteúdo de melatonina retiniana devido à redução da atividade da AANAT causada pela queda no conteúdo de AMPc. O tratamento com insulina restabeleceu tanto o perfil de atividade da AANAT quanto à síntese de melatonina. Supõe-se que as retinas dos animais diabéticos estão mais vulneráveis aos danos decorrentes do quadro diabético, já que a síntese da melatonina está diminuída.Melatonin controls several retinal physiologic rhythmic phenomena besides being the most powerful natural free radical scavenger. The aim of this work is evaluating the retinal melatonin diurnal profile of diabetic rats. Male Wistar rats were diabetic-induced by an injection of STZ and some of them were treated with insulin (6U/day). Retinas were obtained throughout the 24h light-dark cycle for retinal melatonin content, enzymes activity, cAMP content and gene expression analysis. Control animals showed a retinal melatonin daily rhythm with high levels at night while diabetic rats presented a reduction. The AANAT activity showed a daily rhythm with high levels at night in the control group. This daily fluctuation was vanished in STZ-induced diabetic rats and insulin-treatment restored both parameters. We suppose the AANAT activity reduction observed is due to the reduced cAMP content. As melatonin plays an important role modulating circadian functions, this impairment could compromise the retinal physiological homeostasis

Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats

Retinal melatonin synthesis occurs in the photoreceptor layer in a circadian manner, controlling several physiologic rhythmic phenomena, besides being the most powerful natural free radical scavenger. The purpose of the present work was to evaluate the diurnal profile of retinal melatonin content and the regulation of its synthesis in the retina of streptozotocin-induced diabetic rats.status: publishe

A Short-Day Photoperiod Delays the Timing of Puberty in Female Mice via Changes in the Kisspeptin System

The reproduction of seasonal breeders is modulated by exposure to light in an interval of 24 h defined as photoperiod. The interruption of reproductive functions in seasonally breeding rodents is accompanied by the suppression of the Kiss1 gene expression, which is known to be essential for reproduction. In non-seasonal male rodents, such as rats and mice, short-day photoperiod (SP) conditions or exogenous melatonin treatment also have anti-gonadotropic effects; however, whether photoperiod is able to modulate the puberty onset or Kiss1 gene expression in mice is unknown. In the present study, we investigated whether photoperiodism influences the sexual maturation of female mice via changes in the kisspeptin system. We observed that SP condition delayed the timing of puberty in female mice, decreased the hypothalamic expression of genes related to the reproductive axis and reduced the number of Kiss1-expressing neurons in the rostral hypothalamus. However, SP also reduced the body weight gain during development and affected the expression of neuropeptides involved in the energy balance regulation. When body weight was recovered via a reduction in litter size, the timing of puberty in mice born and raised in SP was advanced and the effects in hypothalamic mRNA expression were reverted. These results suggest that the SP delays the timing of puberty in female mice via changes in the kisspeptin system, although the effects on hypothalamic–pituitary–gonadal axis are likely secondary to changes in body weight gain

Modulation of Bone Morphogenetic Protein-9 Expression and Processing by Insulin, Glucose, and Glucocorticoids: Possible Candidate for Hepatic Insulin-Sensitizing Substance

Bone morphogenetic protein 9 (BMP-9), a member of the TGF-beta superfamily predominantly expressed in nonparenchymal liver cells, has been demonstrated to improve glucose homeostasis in diabetic mice. Along with this therapeutic effect, BMP-9 was proposed as a candidate for the hepatic insulin-sensitizing substance ( HISS). Whether BMP-9 plays a physiological role in glucose homeostasis is still unknown. In the present study, we show that BMP-9 expression and processing is severely reduced in the liver of insulin-resistant rats. BMP-9 expression and processing was directly stimulated by in situ exposition of the liver to the combination of glucose and insulin and oral glucose in overnight fasted rats. Additionally, prolonged fasting ( 72 h) abrogated refeeding-induced BMP-9 expression and processing. Previous exposition to dexamethasone, a known inductor of insulin resistance, reduced BMP-9 processing stimulated by the combination of insulin and glucose. Finally, we show that neutralization of BMP-9 with an anti-BMP-9 antibody induces glucose intolerance and insulin resistance in 12-h fasted rats. Collectively, the present results demonstrate that BMP-9 plays an important role in the control of glucose homeostasis of the normal rat. Additionally, BMP-9 is expressed and processed in an HISS-like fashion, which is impaired in the presence of insulin resistance. BMP-9 regulation according to the feeding status and the presence of diabetogenic factors reinforces the hypothesis that BMP-9 might exert the role of HISS in glucose homeostasis physiology. ( Endocrinology 149: 6326-6335, 2008)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNPq Conselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPES