RESUMEN
Reading nutrition facts labels is a competency for which training is given in several nutrition education programs, especially in obesity outreach workshops. The Top Trumps-style card game is commonly used in obesity prevention educational programs to engage participants in reading nutrition facts labels; however, the success of TV cooking shows among children and teenagers has not been explored for educational purposes. This paper is a descriptive study of developing a gamified activity as part of the one-time outreach workshop facilitated by the Obesity and Comorbidities Research Center (OCRC) in Brazil. By playing the MestreChef Nutritional (MCN) game, participants followed similar rules as the corresponding TV cooking show. They were challenged to decide to select food items, calculate dietary food intake, and prepare a recipe to visualize the proportion of macronutrients contained in daily diets. The analysis of the nutritional dietary table completed by participants revealed to be a rich source of information, and we identified in our cohort that selecting an adequate number of food items and making healthy food choices was not concerning. However, their lack of competency in performing mathematical reasoning, particularly in calculating serving sizes and converting grams of macronutrients into calories, was evident. Moreover, facilitators of the workshops agreed that the MCN game presents definitively more didactic effectiveness and playability than the Foods Top Trumps, a former game used in the outreach workshops. The MCN game nourishes the engagement of the participants in learning nutrition-related concepts and may be an efficient didactic resource to improve nutrition knowledge in outreach activities when an alternative method is required to stimulate reading nutrition facts labels.NEW & NOTEWORTHY Reading nutrition facts labels is a typical activity promoted in obesity prevention educational programs. By playing the MestreChef Nutritional, participants can immerse in the context of a food TV show game to have the first contact with reading nutrition facts labels for a learning purpose. However, the game can reveal the participant's limitations in mathematical reasoning despite the didactic potential of the game in promoting obesity-related physiology concepts.
Asunto(s)
Dieta , Educación en Salud , Adolescente , Niño , Humanos , Educación en Salud/métodos , Etiquetado de Alimentos/métodos , Ingestión de Energía , Obesidad/prevención & control , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Traditional lab classes in microbiology are common in several educational institutions, which can provide a learning experience disconnected from the myriad of experiments performed in research laboratories. Attempting to promote an authentic learning opportunity of the functioning of a bacteriology research laboratory, we developed the "Real-Lab-Day," a multimodal learning experience to develop competencies, abilities, critical analysis, and teamwork skills for undergraduate students. Students were divided into groups and assigned to research laboratories to be mentored by graduate students, to design and carry out scientific assays. Undergraduate students were introduced to methods such as cellular and molecular assays, flow cytometry, and fluorescence microscopy, as tools to address scientific questions about bacterial pathogenicity, bacterial resistance, and other topics. To consolidate their learning, students created and presented a poster in a rotational panel of peer learning. The perceived learning and interest in microbiology research were improved by the Real-Lab-Day experience, and >95% of the students approved the Real-Lab-Day as a teaching tool in microbiology. Students exposed to a research laboratory had a positive experience with the teaching method, and over 90% saw it as beneficial to improve their understanding of the scientific concepts discussed during lectures. Likewise, their interest in pursuing a career in microbiology was stimulated by the Real-Lab-Day experience. In conclusion, this educational initiative depicts an alternative methodology to connect students to the research and offers an opportunity to be in close contact with experts and graduate students, who gain teaching experience.
Asunto(s)
Curriculum , Educación de Pregrado en Medicina , Humanos , Aprendizaje , Estudiantes , Instituciones Académicas , Educación de Pregrado en Medicina/métodos , Microbiología/educaciónRESUMEN
Using real-world situations to engage students in learning specific content is advocated by educational research as an effective strategy. However, motivating students to establish personal and emotional connections with the curricular content is challenging. We presented a didactic strategy named "the presidential election of the human body," created to use the presidential election context to engage students in studying cell function and structure using role-playing and appropriation of scientific concepts. Four groups of students (n = 124) of the science and mathematics teacher training program chose a cell of the human body to impersonate, they studied the biology of their cell, and they ran in a presidential election campaign. They created slogans, videos, and materials for their campaign, and on the day of the election the group of students voted for the best slogan. The didactic strategy was capable of stimulating the appropriation of the characteristics of the cells they represented. The majority (75%) of the elected candidates represented cells that are linked to the nervous system. Musicality and humor were the most frequent styles that appeared in the slogans. Students strongly agreed that they enjoyed the activity and considered it valuable for contextualizing the learning of anatomy and physiology. Thus, the activity is a didactic resource to stimulate the students to embrace the content they are learning in the contextualized momentum of a presidential election.
Asunto(s)
Cuerpo Humano , Fisiología/educación , Estudiantes , Enseñanza , Curriculum , Humanos , Aprendizaje , PolíticaRESUMEN
The Internet has changed the way teachers and students access information and build knowledge. The recent COVID-19 pandemic has created challenges for both teachers and students and a demand for new methodologies of remote learning. In the life sciences, mixing online content with practical activities represents an even greater challenge. In microbiology, the implementation of an active teaching methodology, the #Adopt project, based on the social network Facebook®, represents an excellent option for connecting remote education with classroom activities. In 2020, the version applied in high school, "Adopt a Microorganism", was adapted to meet the demands of emergency remote education owing to the suppression of face-to-face activities caused by the pandemic. In the present study, we assessed how the change in methodology impacted the discourse richness of students from high school integrated with technical education in the Business Administration program of the Federal Institute of São Paulo, Sorocaba Campus. Three questionnaires related to the groups of microorganisms (Archaea, Bacteria, Virus, Fungi, and Protozoan) were applied. The students' responses in the 2019 and 2020 classes were compared concerning content richness and multiplicity of concepts through the application of the Shannon diversity index, an approach that is generally used to assess biodiversity in different environments. The observed results suggest that remote learning provided students with a conceptual basis and richness of content equivalent to that achieved by students subjected to the hybrid teaching model. In conclusion, this study suggests that the #Adopt project methodology increases students' discourse richness in microbiology even without face-to-face traditional classes.
Asunto(s)
COVID-19/epidemiología , Educación a Distancia/métodos , Microbiología/educación , Instituciones Académicas/organización & administración , Estudiantes/psicología , Enseñanza/organización & administración , COVID-19/virología , Humanos , Aprendizaje , SARS-CoV-2/fisiología , Encuestas y CuestionariosRESUMEN
Remote education has become necessary to resume teaching activities during the pandemic. Most educators were not prepared for this type of teaching or did not have access to the resources required for online classes. Taking advantage of the sudden interest in the microbial world, we developed Outbreak!, a board game that can be used to support hybrid teaching, focusing on transmission and symptoms caused by viral diseases. We used the engaging potential of cooperative board games to provoke an enriching debate about the roles of both researchers and health workers during an outbreak. Educators in developing countries are in desperate need of creative and accessible tools during this unprecedented crisis. We believe Outbreak! can be a useful and fun tool.
RESUMEN
Online and distance education may be dismissed by educators who argue that these methods are not equivalent to traditional face-to-face education due to the lack of laboratory classes. However, smartphone-assisted experimentation is an innovative and powerful didactic tool that helps educators in the teaching process of physiology, particularly in situations with a lack of financial support for purchasing laboratory equipment, or lack of support for homework and assignments, distance learning courses, and emergency remote education, such as during the COVID-19 pandemic. Therefore, we present the concept of the mobile learning laboratory (MobLeLab), which is a collection of smartphone applications that allow scientific data collection, such as physiological variables, for educational purposes. The three types of MobLeLabs (simulators, built-in, and plug-in) are presented, as well as ideas on how to use smartphone sensors to collect physiological data. Additionally, we elaborate on the principles of the protocols for physiology education with MobLeLabs and discuss their importance to fostering scientific method reasoning by students.
Asunto(s)
Educación a Distancia/métodos , Aplicaciones Móviles , Fisiología/educación , Teléfono Inteligente , Enseñanza , COVID-19 , Infecciones por Coronavirus , Humanos , Pandemias , Neumonía ViralRESUMEN
Physiology teaching resources have advanced to include innovative pedagogical approaches that meet the learning expectations of the current generation of students, while at the same time ensuring content delivery is accurate and the use of technologies is appropriate. We developed a quick experimental assay protocol to introduce the basic concepts of cardiac rhythms, and to demonstrate simultaneously that smartphone applications are a reliable and cost-effective tool for data collection in teaching the scientific method and performing physiology activities. The cardiac rhythm dance (CRD) protocol engages students in dancing a cardiac cyclelike movement to the rhythm of classical, pop, and samba music, and measuring their own cardiac frequency. Students collected their own data using the app Instant Heart Rate (Azumio). The CRD protocol allowed students to conclude that cardiac cycle-like movements paced by a pop song could represent the normal cardiac rhythm, whereas a classical song induced a significant reduction of heart rate, and the samba song significantly increased heart rate compared with the pop song. After group discussion, students considered that the pop rhythm is more realistic of day-by-day movement rhythms and is equivalent to the steady state of daily cardiac rhythms. Students considered the bradycardic and tachycardic movements to the dancing performed to the classical and samba rhythms, respectively. Thus the CRD protocol provides a multiple sensory-based and active learning resource that can engage students in learning cardiovascular physiology and recognizes smartphones as scientific instruments for collecting data during hands-on activities.
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Sistema Cardiovascular , Instrucción por Computador/instrumentación , Baile , Educación Profesional , Frecuencia Cardíaca , Periodicidad , Fisiología/educación , Teléfono Inteligente , Comprensión , Instrucción por Computador/métodos , Curriculum , Educación Profesional/métodos , Escolaridad , Humanos , Aprendizaje , Estudiantes/psicologíaRESUMEN
Cost-effective student engagement poses a challenge for instructors, especially those who may not be familiar with new technologies and mobile devices. In this workshop, participants, experienced and discussed two ways of using smartphones in physiology classes: to engage in an online learning environment for discussions, and to make physiological measurements. Participants signed up for individual Twitter accounts and learned how to tweet, retweet, message, use a URL shortener, and use hashtags. They then went on to locate articles on an assigned topic from the Twitter accounts of credible science sources ( American Journal of Physiology, The Scientist, CDC.gov, WHO.int) and applied their Twitter skills to discuss the science topic of current interest. Additionally, participants shared their knowledge about the use of smartphones as a tool for teaching; they discussed the foundations of smartphone-assisted learning and the concept of mobile-learning laboratories, which we refer to as MobLeLabs. Participants also performed an experiment that used an Axé dance video and smartphone applications to measure changes in heart rate and reaction time. Our report describes this international hands-on teaching workshop and highlights its outcomes.
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Educación/tendencias , Empleos en Salud/educación , Aprendizaje , Informe de Investigación/tendencias , Teléfono Inteligente/tendencias , Medios de Comunicación Sociales/tendencias , Brasil , Educación/métodos , Humanos , Estudiantes del Área de la SaludRESUMEN
We investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX. These modulations were accompanied by accumulation of hepatic triglycerides (TG). Sixty-hour fasted DEX also showed increased citrate synthase (CS) activity, ATP citrate lyase (ACLY) content, and pyruvate kinase 2 (pkm2), glucose transporter 1 (slc2a1) and lactate dehydrogenase-a (ldha) expressions. Hepatic AKT2 was increased in 60-hour fasted DEX, in parallel with reduced miRNAs targeting the AKT2 gene. Altogether, we show that metabolic programming by prenatal dexamethasone is characterized by an unexpected hepatic TG accumulation during prolonged fasting. The underlying mechanism may depend on increased hepatic glycolytic flux due to increased pkm2 expression and consequent conversion of pyruvate to non-esterified fatty acid synthesis due to increased CS activity and ACLY levels. Upregulation of AKT2 due to reduced miRNAs may serve as a permanent mechanism leading to increased pkm2 expression.
Asunto(s)
Dexametasona/farmacología , Ayuno/metabolismo , Hígado/metabolismo , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Triglicéridos/metabolismo , Animales , Biomarcadores , Femenino , Glucosa/metabolismo , Intolerancia a la Glucosa , Pruebas de Función Hepática , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Factores de TiempoRESUMEN
Despite its common use, the synthetic glucocorticoid dexamethasone can cause several adverse effects, such as diabetes and insulin-related metabolic impairment. Thus, research on molecules that could provide the same anti-inflammatory response with milder side effects is constant. In this work the anti-inflammatory activity of the natural sesquiterpene polygodial, extracted from the endemic Brazilian plant Drimys brasiliensis Miers (Winteraceae), was investigated. Employing a pancreatic ß-cell model (INS 1E), the effect of polygodial on signaling pathways is similar to that caused by dexamethasone - both increased MKP1 and decreased ERK1/2 expression in a dose-response and time-dependent manner. Relating to such finding, nuclear translocation of the glucocorticoid receptor was also discovered to be induced by the sesquiterpene. Molecular modeling results indicated that polygodial was capable of docking to the glucocorticoid receptor, but presented preference for the Arg611 binding site rather than Thr739 when set to bind freely inside the pocket. At last, fragmentation of DNA was verified as consequence of sesquiterpene-induced cell death. Altogether, our results suggest that, like dexamethasone, polygodial interacts the glucocorticoid receptor ligand binding domain but create fewer ligand-protein interactions at the site, yielding a weaker effector response. Such property provides an advantage when regarding the adverse effects resulting from stronger affinity ligands of the glucocorticoid receptor, such as in the case of the current standard dexamethasone-based treatment. This aspect, also, turns polygodial an interesting hit compound to the development of new drugs based on its backbone structure providing less harmful anti-inflammatory treatments.
Asunto(s)
Dexametasona/farmacología , Drimys/química , Glucocorticoides/farmacología , Células Secretoras de Insulina/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Animales , Sitios de Unión , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Dexametasona/química , Células Secretoras de Insulina/efectos de los fármacos , Ratones , Simulación del Acoplamiento Molecular , Transporte de Proteínas/efectos de los fármacos , Receptores de Glucocorticoides/metabolismo , Sesquiterpenos/química , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
Several epidemiological and experimental studies demonstrate that modulation of inflammatory response and oxidative stress by natural phytochemicals is a promising strategy to prevent and treat many chronic inflammatory diseases. Camu-camu is an Amazonian fruit with a high content of antioxidants, especially phenolic compounds and vitamin C. In the present study we evaluated the in vivo effects of chronic ingestion of raw extracts derived from camu-camu (Myrciaria dubia McVaugh) frozen pulp on plasma lipid profile and oxidative stress in streptozotocin-induced diabetic rats. Oral administration of camu-camu raw extracts significantly increased plasma antioxidant activity, reduced triacylglycerol and total cholesterol and lipid peroxidation in the plasma of streptozotocin-induced diabetic rats. However, no effect was observed on glucose metabolism of diabetic rats, probably due to the severity of this model.
RESUMEN
Although it is well known that the thyroid hormone (T3) is an important positive regulator of cardiac function over a short term and that it also promotes deleterious effects over a long term, the molecular mechanisms for such effects are not yet well understood. Because most alterations in cardiac function are associated with changes in sarcomeric machinery, the present work was undertaken to find novel sarcomeric hot spots driven by T3 in the heart. A microarray analysis indicated that the M-band is a major hot spot, and the structural sarcomeric gene coding for the M-protein is severely down-regulated by T3. Real-time quantitative PCR-based measurements confirmed that T3 (1, 5, 50, and 100 physiological doses for 2 days) sharply decreased the M-protein gene and protein expression in vivo in a dose-dependent manner. Furthermore, the M-protein gene expression was elevated 3.4-fold in hypothyroid rats. Accordingly, T3 was able to rapidly and strongly reduce the M-protein gene expression in neonatal cardiomyocytes. Deletions at the M-protein promoter and bioinformatics approach suggested an area responsive to T3, which was confirmed by chromatin immunoprecipitation assay. Functional assays in cultured neonatal cardiomyocytes revealed that depletion of M-protein (by small interfering RNA) drives a severe decrease in speed of contraction. Interestingly, mRNA and protein levels of other M-band components, myomesin and embryonic-heart myomesin, were not altered by T3. We concluded that the M-protein expression is strongly and rapidly repressed by T3 in cardiomyocytes, which represents an important aspect for the basis of T3-dependent sarcomeric deleterious effects in the heart.
Asunto(s)
Cardiomegalia/genética , Conectina/genética , Regulación hacia Abajo/genética , Hormonas Tiroideas/farmacología , Animales , Animales Recién Nacidos , Secuencia de Bases , Cardiomegalia/etiología , Cardiomegalia/fisiopatología , Línea Celular , Células Cultivadas , Conectina/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Hipotiroidismo/genética , Masculino , Ratones , Datos de Secuencia Molecular , Contracción Miocárdica/efectos de los fármacos , Contracción Miocárdica/genética , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Unión Proteica/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Hormona Tiroidea/metabolismo , Sarcómeros/metabolismo , Tirotoxicosis/complicaciones , Triyodotironina/farmacología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
A positive relationship between obesity and asthma has been well documented. The AMP-activated protein kinase (AMPK) activator metformin reverses obesity-associated insulin resistance (IR) and inhibits different types of inflammatory responses. This study aimed to evaluate the effects of metformin on the exacerbation of allergic eosinophilic inflammation in obese mice. Male C57BL6/J mice were fed for 10 weeks with high-fat diet (HFD) to induce obesity. The cell infiltration and inflammatory markers in bronchoalveolar lavage (BAL) fluid and lung tissue were evaluated at 48 h after ovalbumin (OVA) challenge. HFD obese mice displayed peripheral IR that was fully reversed by metformin (300 mg/kg/day, two weeks). OVA-challenge resulted in higher influx of total cell and eosinophils in lung tissue of obese mice compared with lean group. As opposed, the cell number in BAL fluid of obese mice was reduced compared with lean group. Metformin significantly reduced the tissue eosinophil infiltration and prevented the reduction of cell counts in BAL fluid. In obese mice, greater levels of eotaxin, TNF-α and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin. In addition, metformin nearly abrogated the binding of NF-κB subunit p65 to the iNOS promoter gene in lung tissue of obese mice. Lower levels of phosphorylated AMPK and its downstream target acetyl CoA carboxylase (ACC) were found in lung tissue of obese mice, which were restored by metformin. In separate experiments, the selective iNOS inhibitor aminoguanidine (20 mg/kg, 3 weeks) and the anti-TNF-α mAb (2 mg/kg) significantly attenuated the aggravation of eosinophilic inflammation in obese mice. In conclusion, metformin inhibits the TNF-α-induced inflammatory signaling and NF-κB-mediated iNOS expression in lung tissue of obese mice. Metformin may be a good pharmacological strategy to control the asthma exacerbation in obese individuals.
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Asma/complicaciones , Inflamación/prevención & control , Metformina/farmacología , Obesidad/complicaciones , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Western Blotting , Líquido del Lavado Bronquioalveolar/citología , Dieta Alta en Grasa/efectos adversos , Inhibidores Enzimáticos/farmacología , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Eosinófilos/patología , Guanidinas/farmacología , Hipoglucemiantes/farmacología , Inflamación/etiología , Resistencia a la Insulina , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Obesidad/etiología , Obesidad/metabolismo , Ovalbúmina/farmacología , Regiones Promotoras Genéticas/genética , Unión Proteica , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients.
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Antioxidantes/farmacología , Gluconeogénesis/efectos de los fármacos , Hipotálamo/metabolismo , Hígado/metabolismo , Melatonina/farmacología , Proteína Oncogénica v-akt/metabolismo , Receptor de Melatonina MT1/efectos de los fármacos , Receptor de Melatonina MT2/efectos de los fármacos , Animales , Western Blotting , Técnica del Anticuerpo Fluorescente , Prueba de Tolerancia a la Glucosa , Hipotálamo/efectos de los fármacos , Inyecciones Intraventriculares , Hígado/efectos de los fármacos , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Ácido Pirúvico/metabolismo , Ratas , Ratas Wistar , Receptores Muscarínicos/efectos de los fármacosRESUMEN
BACKGROUND: Shift work was recently described as a factor that increases the risk of Type 2 diabetes mellitus. In addition, rats born to mothers subjected to a phase shift throughout pregnancy are glucose intolerant. However, the mechanism by which a phase shift transmits metabolic information to the offspring has not been determined. Among several endocrine secretions, phase shifts in the light/dark cycle were described as altering the circadian profile of melatonin production by the pineal gland. The present study addresses the importance of maternal melatonin for the metabolic programming of the offspring. METHODOLOGY/PRINCIPAL FINDINGS: Female Wistar rats were submitted to SHAM surgery or pinealectomy (PINX). The PINX rats were divided into two groups and received either melatonin (PM) or vehicle. The SHAM, the PINX vehicle and the PM females were housed with male Wistar rats. Rats were allowed to mate and after weaning, the male and female offspring were subjected to a glucose tolerance test (GTT), a pyruvate tolerance test (PTT) and an insulin tolerance test (ITT). Pancreatic islets were isolated for insulin secretion, and insulin signaling was assessed in the liver and in the skeletal muscle by western blots. We found that male and female rats born to PINX mothers display glucose intolerance at the end of the light phase of the light/dark cycle, but not at the beginning. We further demonstrate that impaired glucose-stimulated insulin secretion and hepatic insulin resistance are mechanisms that may contribute to glucose intolerance in the offspring of PINX mothers. The metabolic programming described here occurs due to an absence of maternal melatonin because the offspring born to PINX mothers treated with melatonin were not glucose intolerant. CONCLUSIONS/SIGNIFICANCE: The present results support the novel concept that maternal melatonin is responsible for the programming of the daily pattern of energy metabolism in their offspring.
Asunto(s)
Metabolismo Energético/fisiología , Melatonina/fisiología , Animales , Femenino , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Resistencia a la Insulina , Embarazo , Resultado del Embarazo , Ratas , Ratas Wistar , Transducción de SeñalRESUMEN
Quercetin is a potent anti-inflammatory flavonoid, but its capacity to modulate insulin sensitivity in obese insulin resistant conditions is unknown. This study investigated the effect of quercetin treatment upon insulin sensitivity of ob/ob mice and its potential molecular mechanisms. Obese ob/ob mice were treated with quercetin for 10 weeks, and L6 myotubes were treated with either palmitate or tumor necrosis factor-α (TNFα) plus quercetin. Cells and muscles were processed for analysis of glucose transporter 4 (GLUT4), TNFα and inducible nitric oxide synthase (iNOS) expression, and c-Jun N-terminal kinase (JNK) and inhibitor of nuclear factor-κB (NF-κB) kinase (IκK) phosphorylation. Myotubes were assayed for glucose uptake and NF-κB translocation. Chromatin immunoprecipitation assessed NF-κB binding to GLUT4 promoter. Quercetin treatment improved whole body insulin sensitivity by increasing GLUT4 expression and decreasing JNK phosphorylation, and TNFα and iNOS expression in skeletal muscle. Quercetin suppressed palmitate-induced upregulation of TNFα and iNOS and restored normal levels of GLUT4 in myotubes. In parallel, quercetin suppressed TNFα-induced reduction of glucose uptake in myotubes. Nuclear accumulation of NF-κB in myotubes and binding of NF-κB to GLUT4 promoter in muscles of ob/ob mice were also reduced by quercetin. We demonstrated that quercetin decreased the inflammatory status in skeletal muscle of obese mice and in L6 myotubes. This effect was followed by increased muscle GLUT4, with parallel improvement of insulin sensitivity. These results point out quercetin as a putative strategy to manage inflammatory-related insulin resistance.
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Mediadores de Inflamación/antagonistas & inhibidores , Insulina/fisiología , Fibras Musculares Esqueléticas/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Quercetina/farmacología , Animales , Antioxidantes/farmacología , Regulación hacia Abajo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/prevención & control , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Obesos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Quercetina/uso terapéutico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The transition from gestation to lactation is characterized by a robust adaptation of maternal pancreatic ß-cells. Consistent with the loss of ß-cell mass, glucose-induced insulin secretion is down-regulated in the islets of early lactating dams. Extensive experimental evidence has demonstrated that the surge of prolactin is responsible for the morphofunctional remodeling of the maternal endocrine pancreas during pregnancy, but the precise molecular mechanisms by which this phenotype is rapidly reversed after delivery are not completely understood. This study investigated whether glucocorticoid-regulated expression of Rasd1/Dexras, a small inhibitory G protein, is involved in this physiological plasticity. Immunofluorescent staining demonstrated that Rasd1 is localized within pancreatic ß-cells. Rasd1 expression in insulin-secreting cells was increased by dexamethasone and decreased by prolactin. In vivo data confirmed that Rasd1 expression is decreased in islets from pregnant rats and increased in islets from lactating mothers. Knockdown of Rasd1 abolished the inhibitory effects of dexamethasone on insulin secretion and the protein kinase A, protein kinase C, and ERK1/2 pathways. Chromatin immunoprecipitation experiments revealed that glucocorticoid receptor (GR) and signal transducer and activator of transcription 5b (STAT5b) cooperatively mediate glucocorticoid-induced Rasd1 expression in islets. Prolactin inhibited the stimulatory effect of GR/STAT5b complex on Rasd1 transcription. Overall, our data indicate that the stimulation of Rasd1 expression by glucocorticoid at the end of pregnancy reverses the increased insulin secretion that occurs during pregnancy. Prolactin negatively regulates this pathway by inhibiting GR/STAT5b transcriptional activity on the Rasd1 gene.
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Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Periodo Periparto/metabolismo , Prolactina/farmacología , Proteínas ras/metabolismo , Animales , Western Blotting , Línea Celular , Inmunoprecipitación de Cromatina , Corticosterona/metabolismo , Dexametasona/farmacología , Femenino , Inmunoprecipitación , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Reacción en Cadena de la Polimerasa , Ratas , Ratas Wistar , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/metabolismo , Transducción de Señal/efectos de los fármacos , Transcortina/genética , Transcortina/metabolismo , Proteínas ras/genéticaRESUMEN
Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis through mechanisms that are not completely understood. Recent studies demonstrated that the activation of hypothalamic 5'-AMP-activated protein kinase (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the present study was designed to investigate whether hypothalamic AMPK activation by fructose would mediate increased gluconeogenesis. Both ip and intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as well as in the paraventricular nucleus and the arcuate nucleus. These effects were mimicked by icv 5-amino-imidazole-4-carboxamide-1-ß-d-ribofuranoside treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with injection of a small interfering RNA targeted to AMPKα2 in the mediobasal hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found that fructose increased corticosterone levels through a mechanism that is dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to the PEPCK gene were suppressed by pharmacological glucocorticoid receptor blockage. Altogether the data presented herein support the hypothesis that fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis by increasing corticosterone levels.
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Proteínas Quinasas Activadas por AMP/metabolismo , Corticosterona/metabolismo , Fructosa/farmacología , Gluconeogénesis/efectos de los fármacos , Hipotálamo/metabolismo , Hígado/metabolismo , Animales , Inmunoprecipitación de Cromatina , Activación Enzimática/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Hipotálamo/efectos de los fármacos , Immunoblotting , Hígado/efectos de los fármacos , Masculino , Fosfoenolpiruvato Carboxiquinasa (ATP) , Fosforilación/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Thyroid diseases are prevalent among endocrine disorders, and careful evaluation of patients' symptoms is a very important part in their diagnosis. Developing new pedagogical strategies, such as problem-based learning (PBL), is extremely important to stimulate and encourage medical and biomedical students to learn thyroid physiology and identify the signs and symptoms of thyroid dysfunction. The present study aimed to create a new pedagogical approach to build deep knowledge about hypo-/hyperthyroidism by proposing a hands-on activity based on a detective case, using alternative materials in place of laboratory animals. After receiving a description of a criminal story involving changes in thyroid hormone economy, students collected data from clues, such as body weight, mesenteric vascularization, visceral fat, heart and thyroid size, heart rate, and thyroid-stimulating hormone serum concentration to solve the case. Nevertheless, there was one missing clue for each panel of data. Four different materials were proposed to perform the same practical lesson. Animals, pictures, small stuffed toy rats, and illustrations were all effective to promote learning, and the detective case context was considered by students as inviting and stimulating. The activity can be easily performed independently of the institution's purchasing power. The practical lesson stimulated the scientific method of data collection and organization, discussion, and review of thyroid hormone actions to solve the case. Hence, this activity provides a new strategy and alternative materials to teach without animal euthanization.
Asunto(s)
Fisiología/educación , Aprendizaje Basado en Problemas/métodos , Enseñanza/métodos , Enfermedades de la Tiroides/sangre , Hormonas Tiroideas/sangre , Animales , Brasil , Escolaridad , Corazón , Frecuencia Cardíaca , Humanos , Grasa Intraabdominal , Masculino , Mesenterio/irrigación sanguínea , Modelos Educacionales , Ratas , Ratas Wistar , Enfermedades de la Tiroides/metabolismo , Hormonas Tiroideas/metabolismo , Hormonas Tiroideas/fisiología , Tirotropina/sangre , Tirotropina/metabolismoRESUMEN
It is known that the circadian rhythm in hepatic phosphoenolpyruvate carboxykinase expression (a limiting catalytic step of gluconeogenesis) and hepatic glucose production is maintained by both daily oscillation in autonomic inputs to the liver and night feeding behavior. However, increased glycemia and reduced melatonin (Mel) levels have been recently shown to coexist in diabetic patients at the end of the night period. In parallel, pinealectomy (PINX) is known to cause glucose intolerance with increased basal glycemia exclusively at the end of the night. The mechanisms that underlie this metabolic feature are not completely understood. Here, we demonstrate that PINX rats show night-time hepatic insulin resistance characterized by reduced insulin-stimulated RAC-α serine/threonine-protein kinase phosphorylation and increased phosphoenolpyruvate carboxykinase expression. In addition, PINX rats display increased conversion of pyruvate into glucose at the end of the night. The regulatory mechanism suggests the participation of unfolded protein response (UPR), because PINX induces night-time increase in activating transcription factor 6 expression and prompts a circadian fashion of immunoglobulin heavy chain-binding protein, activating transcription factor 4, and CCAAT/enhancer-binding protein-homologous protein expression with Zenith values at the dark period. PINX also caused a night-time increase in Tribble 3 and regulatory-associated protein of mammalian target of rapamycin; both were reduced in liver of PINX rats treated with Mel. Treatment of PINX rats with 4-phenyl butyric acid, an inhibitor of UPR, restored night-time hepatic insulin sensitivity and abrogated gluconeogenesis in PINX rats. Altogether, the present data show that a circadian oscillation of UPR occurs in the liver due to the absence of Mel. The nocturnal UPR activation is related with night-time hepatic insulin resistance and increased gluconeogenesis in PINX rats.