Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Int...Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3',5' -cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.展开更多
BACKGROUND： Oxidative stress is recognized as a pivotal effector of several pathogenic processes, including acute pancreatitis. Reactive oxygen species not just cause damage on the main cellular components, but also ...BACKGROUND： Oxidative stress is recognized as a pivotal effector of several pathogenic processes, including acute pancreatitis. Reactive oxygen species not just cause damage on the main cellular components, but also influence the expression of antioxidant system genes. Antioxidant molecules, such as melatonin, could be good candidates for the treatment of this multidimensional disease. The present study was to evaluate the chemopreventive effect of melatonin in a rat model of ceruleininduced acute pancreatitis.METHODS： Four subcutaneous injections of cerulein（20 μg/kg body weight） were given to Wistar rats at two hours intervals;melatonin was injected intraperitoneally（25 mg/kg body weight）30 minutes before each injection of cerulein. Lipid peroxidation,protein oxidation（carbonyl groups）, total antioxidant status,and glutathione peroxidase activity were determined in pancreatic tissue using commercial kits.RESULTS： The chemopreventive administration of melatonin caused a reduction in lipid peroxidation and protein oxidation due to injections of cerulein. Additionally, melatonin treatment was also able to revert glutathione peroxidase activity and total antioxidant status near to control levels, suggesting that melatonin could prevent from oxidative phenomena in the pancreas, such as lipid peroxidation and protein oxidation,and could stimulate, directly or indirectly, the expression of antioxidant enzymes.CONCLUSION： Melatonin, a polyvalent antioxidant, protected the pancreatic damage via the decrease of oxidative stress andincrease of the activities of antioxidant enzymes in ceruleininduced acute pancreatitis.展开更多
基金Supported by Ministry of Education (AP2009-0753, to Dr. Javier Espino)
文摘Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3',5' -cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.
基金supported by grants from MICINNFEDER(BFU2010-15049)Gobierno de Extremadura(Re:GRU10003)Plan of Recruitment and Training of Human Resources on Research of University of Extremadura(1076)
文摘BACKGROUND： Oxidative stress is recognized as a pivotal effector of several pathogenic processes, including acute pancreatitis. Reactive oxygen species not just cause damage on the main cellular components, but also influence the expression of antioxidant system genes. Antioxidant molecules, such as melatonin, could be good candidates for the treatment of this multidimensional disease. The present study was to evaluate the chemopreventive effect of melatonin in a rat model of ceruleininduced acute pancreatitis.METHODS： Four subcutaneous injections of cerulein（20 μg/kg body weight） were given to Wistar rats at two hours intervals;melatonin was injected intraperitoneally（25 mg/kg body weight）30 minutes before each injection of cerulein. Lipid peroxidation,protein oxidation（carbonyl groups）, total antioxidant status,and glutathione peroxidase activity were determined in pancreatic tissue using commercial kits.RESULTS： The chemopreventive administration of melatonin caused a reduction in lipid peroxidation and protein oxidation due to injections of cerulein. Additionally, melatonin treatment was also able to revert glutathione peroxidase activity and total antioxidant status near to control levels, suggesting that melatonin could prevent from oxidative phenomena in the pancreas, such as lipid peroxidation and protein oxidation,and could stimulate, directly or indirectly, the expression of antioxidant enzymes.CONCLUSION： Melatonin, a polyvalent antioxidant, protected the pancreatic damage via the decrease of oxidative stress andincrease of the activities of antioxidant enzymes in ceruleininduced acute pancreatitis.
