RESUMO
Fasting is known to cause physiological changes in the endocrine pancreas, including decreased insulin secretion and increased reactive oxygen species (ROS) production. However, there is no consensus about the long-term effects of intermittent fasting (IF), which can involve up to 24 hours of fasting interspersed with normal feeding days. In the present study, we analyzed the effects of alternate-day IF for 12 weeks in a developing and healthy organism. Female 30-day-old Wistar rats were randomly divided into two groups: control, with free access to standard rodent chow; and IF, subjected to 24-hour fasts intercalated with 24-hours of free access to the same chow. Alternate-day IF decreased weight gain and food intake. Surprisingly, IF also elevated plasma insulin concentrations, both at baseline and after glucose administration collected during oGTT. After 12 weeks of dietary intervention, pancreatic islets displayed increased ROS production and apoptosis. Despite their lower body weight, IF animals had increased fat reserves and decreased muscle mass. Taken together, these findings suggest that alternate-day IF promote ß -cell dysfunction, especially in developing animals. More long-term research is necessary to define the best IF protocol to reduce side effects.
Assuntos
Tecido Adiposo/metabolismo , Ingestão de Alimentos , Jejum/efeitos adversos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Redução de Peso , Tecido Adiposo/patologia , Animais , Apoptose , Jejum/fisiologia , Feminino , Insulina/sangue , Secreção de Insulina , Músculos/metabolismo , Músculos/patologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fatores de TempoRESUMO
Melatonin is a hormone synthesized in the pineal gland, which modulates several functions within the organism, including the synchronization of glucose metabolism and glucose-stimulated insulin secretion (GSIS). Melatonin can mediate different signaling pathways in pancreatic islets through two membrane receptors and via antioxidant or pro-oxidant enzymes modulation. NADPH oxidase (NOX) is a pro-oxidant enzyme responsible for the production of the reactive oxygen specie (ROS) superoxide, generated from molecular oxygen. In pancreatic islets, NOX-derived ROS can modulate glucose metabolism and regulate insulin secretion. Considering the roles of both melatonin and NOX in islets, the aim of this study was to evaluate the association of NOX and ROS production on glucose metabolism, basal and GSIS in pinealectomized rats (PINX) and in melatonin-treated isolated pancreatic islets. Our results showed that ROS content derived from NOX activity was increased in PINX at baseline (2.8 mM glucose), which was followed by a reduction in glucose metabolism and basal insulin secretion in this group. Under 16.7 mM glucose, an increase in both glucose metabolism and GSIS was observed in PINX islets, without changes in ROS content. In isolated pancreatic islets from control animals incubated with 2.8 mM glucose, melatonin treatment reduced ROS content, whereas in 16.7 mM glucose, melatonin reduced ROS and GSIS. In conclusion, our results demonstrate that both basal and stimulated insulin secretion can be regulated by melatonin through the maintenance of ROS homeostasis in pancreatic islets.
Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Melatonina/fisiologia , NADPH Oxidases/metabolismo , Animais , Glucoquinase/genética , Glucose/metabolismo , Transportador de Glucose Tipo 2/genética , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Melatonina/farmacologia , NADPH Oxidases/genética , Glândula Pineal/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismoRESUMO
Mitochondria and NADPH oxidase are important sources of reactive oxygen species in particular the superoxide radical (ROS) in pancreatic islets. These molecules derived from molecular oxygen are involved in pancreatic ß-cells signaling and control of insulin secretion. We examined the involvement of ROS produced through NADPH oxidase in the leucine- and/or glucose-induced insulin secretion by pancreatic islets from fed or 48-hour fasted rats. Glucose-stimulated insulin secretion (GSIS) in isolated islets was evaluated at low (2.8 mM) or high (16.7 mM) glucose concentrations in the presence or absence of leucine (20 mM) and/or NADPH oxidase inhibitors (VAS2870-20 µM or diphenylene iodonium-DPI-5 µM). ROS production was determined in islets treated with dihydroethidium (DHE) or MitoSOX Red reagent for 20 min and dispersed for fluorescence measurement by flow cytometry. NADPH content variation was examined in INS-1E cells (an insulin secreting cell line) after incubation in the presence of glucose (2.8 or 16.7 mM) and leucine (20 mM). At 2.8 mM glucose, VAS2870 and DPI reduced net ROS production (by 30%) and increased GSIS (by 70%) in a negative correlation manner (r = -0.93). At 16.7 mM glucose or 20 mM leucine, both NADPH oxidase inhibitors did not alter insulin secretion neither net ROS production. Pentose phosphate pathway inhibition by treatment with DHEA (75 µM) at low glucose led to an increase in net ROS production in pancreatic islets from fed rats (by 40%) and induced a marked increase (by 144%) in islets from 48-hour fasted rats. The NADPH/NADP+ ratio was increased when INS-1E cells were exposed to high glucose (by 4.3-fold) or leucine (by 3-fold). In conclusion, increased ROS production through NADPH oxidase prevents the occurrence of hypoglycemia in fasting conditions, however, in the presence of high glucose or high leucine levels, the increased production of NADPH and the consequent enhancement of the activity of the antioxidant defenses mitigate the excess of ROS production and allow the secretory process of insulin to take place.
Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Benzoxazóis/farmacologia , Células Cultivadas , Desidroepiandrosterona/farmacologia , Feminino , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Via de Pentose Fosfato/efeitos dos fármacos , Ratos , Ratos Wistar , Triazóis/farmacologiaRESUMO
Se analizan 87 pacientes con EIP aguda tratadas en la Maternidad, Santa Ana, del I.V.S.S. durante el lapso de 5 años, comprendido del año 1963 al 1987. La mayoría de los pacientes mejoraron con el tratamiento médico a base de antibióticos por vía parenteral, siendo los más usados ampicilina, penicilina y gentamicina. Sólo dos pacientes fueron tratadas quirúrgicamente, practicándose en un caso una laparatomía exploradora y en el otro caso un drenaje de absceso del Douglas por colpotomía posterior. La morbilidad fue baja y no hubo casos de mortalidad en esta serie
Assuntos
Humanos , Feminino , Doença Inflamatória Pélvica/patologia , Doença Inflamatória Pélvica/terapia , Penicilinas , Salpingite , Clindamicina , Gentamicinas , Cloranfenicol , AmpicilinaRESUMO
90 pacientes de las comunidades rurales de Charallave y Caucagüita, Estado Miranda, Venezuela, comprendidos entre los 2 y 15 años de edad y a los que se les diagnosticó infectación parasitaria por Ascaris, Tricurias, Necator, o mixta por Ascaris-Trichuria, mediante examen de heces directo y fueron divididos en dos grupos de 45 pacientes cada uno, administrándose a uno Pamoato de Oxantel/Pirantel y a otro Mebendazol. Se evaluó la eficacia del tratamiento con Oxantel/Pirantel frente al Mebendazol realizando exámenes de heces control a los 7 y 21 días de concluidos los tratamientos y se encontró que de los 45 pacientes tratados con Oxantel/Pirantel, 43 (95,55%) presentaron curación a los 7 días y todos (100%) a los 21 días, mientras que en el segundo grupo, tratados con Mebendazol, a los 7 días 30 pacientes (66,66%) estaban curados, persistiendo a los 21 días 10 pacientes (22,22%) no curados. El Pamoato de Oxantel/Pirantel aparece como altamente eficaz en el tratamiento individual y masivo de las parasitosis intestinales más frecuentes en el medio rural venezolano