RESUMO
Due to the high incidence and severity of obesity and its related disorders, it is highly desirable to develop new strategies to treat or even to prevent its development. We have previously described that Ginkgo biloba extract (GbE) improved insulin resistance and reduced body weight gain of obese rats. In the present study we aimed to evaluate the effect of GbE on both inflammatory cascade and insulin signaling in retroperitoneal fat depot of diet-induced obese rats. Rats were fed with high fat diet for 2 months and thereafter treated for 14 days with 500 mg/kg of GbE. Rats were then euthanized and samples from retroperitoneal fat depot were used for western blotting, RT-PCR, and ELISA experiments. The GbE treatment promoted a significant reduction on both food/energy intake and body weight gain in comparison to the nontreated obese rats. In addition, a significant increase of both Adipo R1 and IL-10 gene expressions and IR and Akt phosphorylation was also observed, while NF-κB p65 phosphorylation and TNF-α levels were significantly reduced. Our data suggest that GbE might have potential as a therapy to treat obesity-related metabolic diseases, with special interest to treat obese subjects resistant to adhere to a nutritional education program.
Assuntos
Ginkgo biloba/química , Inflamação/tratamento farmacológico , Insulina/metabolismo , Gordura Intra-Abdominal/patologia , Obesidade/tratamento farmacológico , Extratos Vegetais/química , Animais , Peso Corporal , Dietoterapia , Modelos Animais de Doenças , Ingestão de Energia , Resistência à Insulina , Gordura Intra-Abdominal/efeitos dos fármacos , Masculino , Fosforilação , Fitoterapia , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
Type 2 diabetes mellitus (T2DM) stands as a prevalent global public health issue caused by deficiencies in the action of insulin and/or insulin production. In the liver, insulin plays an important role by inhibiting hepatic glucose production and stimulating glycogen storage, thereby contributing to blood glucose regulation. Kaempferitrin (KP) and kaempferol (KM), flavonoids found in Bauhinia forficata, exhibit insulin-mimetic properties, showing promise in managing T2DM. In this study, we aimed to assess the potential of these compounds in modulating the insulin signaling pathway and/or glucose metabolism. Cell viability assays confirmed the non-cytotoxic nature of both compounds toward HepG2 cells at the concentrations and times evaluated. Theoretical molecular docking studies revealed that KM had the best docking pose with the IR ß subunit when compared to the KP. Moreover, Langmuir monolayer evaluation indicated molecular incorporation for both KM and KP. Specifically, KM exhibited the capability to increase AKT phosphorylation, a key kinase in insulin signaling, regardless of insulin receptor (IR) activation. Notably, KM showed an additional synergistic effect with insulin in activating AKT. In conclusion, our findings suggest the potential of KM as a promising compound for stimulating AKT activation, thereby influencing energy metabolism in T2DM.
RESUMO
Bioactive metabolites from Bauhinia forficata Link (Bf extract) hold therapeutic potential for type 2 diabetes mellitus (T2DM) but the mechanism remains poorly understood. This study aimed to test the extract from Bf leaves obtained by decoction on the prevention of T2DM in vivo. The Bf extract was tested on a streptozotocin-induced T2DM mouse model fed on a high-fat diet. The insulin resistance was attenuated in T2DM animals supplemented with Bf extract, which indicates glucose intolerance reduction and p-AKT/AKT ratio preservation in the gastrocnemius muscle. These observations suggested that Bf extract enhanced glucose uptake. Nevertheless, there was no preservation in ß-cell insulin secretion in Bf extract-treated T2DM mice. Interestingly, the Bf extract reduced body weight gain without affecting total energy intake. Hence, Bf extract has a hypoglycemic effect which could attenuate the development of insulin resistance.
Assuntos
Bauhinia , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt , Hipoglicemiantes , Glucose , Músculo Esquelético/metabolismo , Insulina , Glicemia/metabolismoRESUMO
The parotid gland is the largest salivary gland. It produces watery saliva, rich in proteins (amylase, lysozymes, and antibodies). Due to the gland's morphological cytoarchitecture composed of only serous acini, it contributes almost 50% of total salivary volume upon stimulation. It has been reported that the prevalence of saliva secretion impairments, periodontitis, delayed wound healing, and xerostomia increase in diabetic patients. Herein we evaluated the acute effects of insulin on insulin receptor phosphorylation status and its substrates IRS-1 and IRS-2 in the parotid glands of adult male Wistar rats, using Western blot analyses. We confirmed an acute effect of insulin on IR/IRS/PI3K/Akt and MAPK intracellular pathway activation in the parotid glands of male Wistar rats similar to the classical metabolic targets of the hormone, like the liver.
Assuntos
Insulina/farmacologia , Glândula Parótida , Transdução de Sinais/efeitos dos fármacos , Xerostomia , Animais , Masculino , Glândula Parótida/efeitos dos fármacos , Glândula Parótida/metabolismo , Ratos , Ratos WistarRESUMO
OBJECTIVES: The aim of this study was to evaluate the preventive effects of extra virgin olive oil (EVOO) or flaxseed oil (FO) on dextran sodium sulfate (DSS)-induced acute ulcerative colitis in female mice. METHODS: Eighty C57BL/6J mice of 8-weeks-old were divided in four groups: Control (SO), 10%EVOO, 10%FO and 5%EVOO+5%FO. The oils were given through the AIN-93M diet. After 30 days, animals were divided in four more groups, in which half received 3%DSS in water for 5 days. Body weight loss, bleeding and stool consistency were verified for the Disease Activity Index (DAI). Animals were euthanized and their colon and spleen weighted and measured. Histopathological analysis, the concentrations of TNF-α, IL-1ß, and IL-10 and the iNOS expression were evaluated in the colon samples. RESULTS: Animals that received DSS presented with elevated disease activity index values; increased colon weight-to-length ratio; augmented leukocyte infiltration into the lamina propria and submucosa; and increased production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, and greater inducible nitric oxide synthase expression in the distal colon. Individually or in combination, the oils were not able to reverse or mitigate any of the DSS-induced symptoms or damage. Additionally, the group of animals treated with DSS and supplemented with FO displayed increased spleen weight-to-body weight ratio, and the group that received a combination of EVOO and FO presented increased TNF-α levels compared with the respective control group. CONCLUSION: Consumption of large amounts of EVOO and FO as a treatment for or prevention against ulcerative colitis could potentially elicit unwanted adverse effects.
Assuntos
Colite Ulcerativa , Colite , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/prevenção & controle , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Feminino , Óleo de Semente do Linho , Camundongos , Camundongos Endogâmicos C57BL , Azeite de OlivaRESUMO
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.
Assuntos
Glucocorticoides/farmacologia , Glucose/farmacologia , Fator 2 de Diferenciação de Crescimento/metabolismo , Insulina/farmacologia , Fígado/efeitos dos fármacos , Animais , Western Blotting , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Glucose/administração & dosagem , Intolerância à Glucose , Fator 2 de Diferenciação de Crescimento/genética , Insulina/administração & dosagem , Resistência à Insulina , Fígado/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: Pregnant women have a 2-3 fold higher probability of developing restless legs syndrome (RLS - sleep-related movement disorders) than general population. This study aims to evaluate the behavior and locomotion of rats during pregnancy in order to verify if part of these animals exhibit some RLS-like features. METHODS: We used 14 female 80-day-old Wistar rats that weighed between 200 and 250 g. The rats were distributed into control (CTRL) and pregnant (PN) groups. After a baseline evaluation of their behavior and locomotor activity in an open-field environment, the PN group was inducted into pregnancy, and their behavior and locomotor activity were evaluated on days 3, 10 and 19 of pregnancy and in the post-lactation period in parallel with the CTRL group. The serum iron and transferrin levels in the CTRL and PN groups were analyzed in blood collected after euthanasia by decapitation. RESULTS: There were no significant differences in the total ambulation, grooming events, fecal boli or urine pools between the CTRL and PN groups. However, the PN group exhibited fewer rearing events, increased grooming time and reduced immobilization time than the CTRL group (ANOVA, p<0.05). CONCLUSION: These results suggest that pregnant rats show behavioral and locomotor alterations similar to those observed in animal models of RLS, demonstrating to be a possible animal model of this sleep disorder.
Assuntos
Comportamento Animal , Modelos Animais de Doenças , Atividade Motora , Prenhez/fisiologia , Síndrome das Pernas Inquietas , Animais , Feminino , Gravidez , Ratos , Ratos WistarRESUMO
PURPOSE: Pregnant women have a 2-3 fold higher probability of developing restless legs syndrome (RLS - sleep-related movement disorders) than general population. This study aims to evaluate the behavior and locomotion of rats during pregnancy in order to verify if part of these animals exhibit some RLS-like features. METHODS: We used 14 female 80-day-old Wistar rats that weighed between 200 and 250 g. The rats were distributed into control (CTRL) and pregnant (PN) groups. After a baseline evaluation of their behavior and locomotor activity in an open-field environment, the PN group was inducted into pregnancy, and their behavior and locomotor activity were evaluated on days 3, 10 and 19 of pregnancy and in the post-lactation period in parallel with the CTRL group. The serum iron and transferrin levels in the CTRL and PN groups were analyzed in blood collected after euthanasia by decapitation. RESULTS: There were no significant differences in the total ambulation, grooming events, fecal boli or urine pools between the CTRL and PN groups. However, the PN group exhibited fewer rearing events, increased grooming time and reduced immobilization time than the CTRL group (ANOVA, p<0.05). CONCLUSION: These results suggest that pregnant rats show behavioral and locomotor alterations similar to those observed in animal models of RLS, demonstrating to be a possible animal model of this sleep disorder.
RESUMO
PURPOSE: Pregnant women have a 2-3 fold higher probability of developing restless legs syndrome (RLS – sleep-related movement disorders) than general population. This study aims to evaluate the behavior and locomotion of rats during pregnancy in order to verify if part of these animals exhibit some RLS-like features. METHODS: We used 14 female 80-day-old Wistar rats that weighed between 200 and 250 g. The rats were distributed into control (CTRL) and pregnant (PN) groups. After a baseline evaluation of their behavior and locomotor activity in an open-field environment, the PN group was inducted into pregnancy, and their behavior and locomotor activity were evaluated on days 3, 10 and 19 of pregnancy and in the post-lactation period in parallel with the CTRL group. The serum iron and transferrin levels in the CTRL and PN groups were analyzed in blood collected after euthanasia by decapitation. RESULTS: There were no significant differences in the total ambulation, grooming events, fecal boli or urine pools between the CTRL and PN groups. However, the PN group exhibited fewer rearing events, increased grooming time and reduced immobilization time than the CTRL group (ANOVA, p<0.05). CONCLUSION: These results suggest that pregnant rats show behavioral and locomotor alterations similar to those observed in animal models of RLS, demonstrating to be a possible animal model of this sleep disorder. .
OBJETIVO: Mulheres grávidas apresentam de duas a trêz vezes maior probabilidade de desenvolver a Síndrome das Pernas Inquietas (SPI – distúrbio do movimento relacionado ao sono) do que a população geral. O objetivo do estudo foi avaliar o comportamento e a locomoção de ratas durante a gravidez, a fim de verificar se esses animais apresentam algumas características SPI-like. MÉTODOS: Foram utilizadas 14 fêmeas Wistar de 80 dias de idade, pesando entre 200 e 250 g. Os ratos foram distribuídos em grupos controle (CTRL) e prenhes (PN). Após uma avaliação inicial do comportamento e da atividade locomotora em um ambiente de campo aberto, o grupo PN foi introduzido a prenhez, e sua atividade e comportamento locomotor foram avaliados nos dias 3, 10 e 19 de prenhez e no período pós-lactação em paralelo ao grupo CTRL. Os níveis de ferro e transferrina séricos nos grupos CTRL e PN foram analisados em sangue coletado após eutanásia por decapitação. RESULTADOS: Não houve diferenças significativas na deambulação total, nos eventos de grooming, bolos fecais e urina entre os grupos CTRL e PN. No entanto, o grupo PN apresentou menos eventos de rearing, aumento no tempo de duração de grooming e redução no tempo de imobilização em relação ao grupo CTRL (ANOVA, p<0,05). CONCLUSÃO: Esses resultados sugerem que ratas prenhes apresentam alterações comportamentais e locomotoras semelhantes às observadas em modelos animais de SPI, demonstrando ser um possível modelo animal desse distúrbio do sono. .