RESUMO
The pinealgland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes. Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different agedmale and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.
RESUMO
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.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Hiperglicemia/metabolismo , Melatonina/análogos & derivados , Animais , Arilalquilamina N-Acetiltransferase/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental/complicações , Humanos , Hiperglicemia/etiologia , Masculino , Melatonina/metabolismo , Microdiálise , Glândula Pineal/metabolismo , Ratos , Ratos WistarRESUMO
The presence of high voltage-activated calcium channels in the rat pineal gland is well known. However, their role in pineal metabolism is not completely understood and is even controversial. Better to understand this matter, we investigated the effects of L-, N- or P/Q-type calcium channel blockers (nifedipine, omega-conotoxin GVIA, omega-agatoxin IVA, respectively) on melatonin content and arylalkylamine-N-acetyltransferase activity of denervated rat pineal glands kept for 48 h in culture and stimulated with norepinephrine. Melatonin was measured by high performance liquid chromatography with electrochemical detection and arylalkylamine-N-acetyltransferase activity was quantified by radiometric assay. Pre-incubation with any of these high voltage-activated calcium channel blockers reduced the melatonin production induced by norepinephrine although arylalkylamine-N-acetyltransferase activity was reduced only by the N-type calcium channel antagonist, omega-conotoxin GVIA. The results indicate that calcium influx through L-, N- or P/Q-type of high voltage-activated calcium channels is necessary for the full expression of the metabolic process leading to melatonin synthesis in the rat pineal glands. However, the mechanisms involved in this process are different for the L- or P/Q- and N-type calcium channels.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Melatonina/biossíntese , Glândula Pineal/metabolismo , Animais , Arilalquilamina N-Acetiltransferase/efeitos dos fármacos , Arilalquilamina N-Acetiltransferase/metabolismo , Canais de Cálcio/metabolismo , Relação Dose-Resposta a Droga , Masculino , Melatonina/análise , Nifedipino/farmacologia , Norepinefrina/farmacologia , Técnicas de Cultura de Órgãos , Glândula Pineal/efeitos dos fármacos , Ratos , Ratos Wistar , ômega-Agatoxina IVA/farmacologia , ômega-Conotoxina GVIA/farmacologiaRESUMO
Two experimental models were tried in young molnourished rats in order to study effect of an hyperosmolar challenge in the small intestine on the bi-diretcional fluxes of sodium. Wealning rats were with emergy restricted diets. In model I 1mL of NaCl900 mOsm/kg was introduced in the smal intestine of the rats left from 5 up to 70 min, in order to determine the moment of higher net Na secretion, which occurred at 10 min. In model II, the bi-directional fluxes of Na and Cl- were studied using Na Cl or mannitol 900 mOsm/kg under the effect of mecholil, atropine or 2-4 dinitrophenol, for 10 min. Mecholil decreased the Na absorption enhancing the net secretion. Control rats were used as reference. In the restricted diets animals occurred an increase of the net secretion stimulated by NaCl 900 mOsm/kg, and this effect was enhanced by mecholil. It is suggested that in malnutrition there is an impairment in Na- intestinal absorption.