RESUMO
Impaired insulin production and/or secretion by pancreatic beta cells can lead to high blood glucose levels and type 2 diabetes (T2D). Therefore, investigating new proteins involved in beta cell response to stress conditions could be useful in finding new targets for therapeutic approaches. KH-type splicing regulatory protein (KSRP) is a protein usually involved in gene expression due to its role in post-transcriptional regulation. Although there are studies describing the important role of KSRP in tissues closely related to glucose homeostasis, its effect on pancreatic beta cells has not been explored so far. Pancreatic islets from diet-induced obese mice (C57BL/6JUnib) were used to determine KSRP expression and we also performed in vitro experiments exposing INS-1E cells (pancreatic beta cell line) to different stressors (palmitate or cyclopiazonic acid-CPA) to induce cellular dysfunction. Here we show that KSRP expression is reduced in all the beta cell dysfunction models tested. In addition, when manipulated to knock down KSRP, beta cells exhibited increased death and impaired insulin secretion, whereas KSRP overexpression prevented cell death and increased insulin secretion. Taken together, our findings suggest that KSRP could be an important target to protect beta cells from impaired functioning and death.
Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Animais , Camundongos , Sobrevivência Celular , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Since their discovery in 2000, there has been a continuous expansion of studies investigating the physiology, biochemistry, and pharmacology of endocrine fibroblast growth factors (FGFs). FGF19, FGF21, and FGF23 comprise a subfamily with attributes that distinguish them from typical FGFs, as they can act as hormones and are, therefore, referred to as endocrine FGFs. As they participate in a broad cross-organ endocrine signaling axis, endocrine FGFs are crucial lipidic, glycemic, and energetic metabolism regulators during energy availability fluctuations. They function as powerful metabolic signals in physiological responses induced by metabolic diseases, like type 2 diabetes and obesity. Pharmacologically, FGF19 and FGF21 cause body weight loss and ameliorate glucose homeostasis and energy expenditure in rodents and humans. In contrast, FGF23 expression in mice and humans has been linked with insulin resistance and obesity. Here, we discuss emerging concepts in endocrine FGF signaling in the brain and critically assess their putative role as therapeutic targets for treating metabolic disorders.
Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Humanos , Animais , Camundongos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Homeostase , Encéfalo/metabolismo , Obesidade/tratamento farmacológicoRESUMO
The development of clinically viable metformin analogs is a challenge largely to be overcome. Despite being an extremely efficient drug for the treatment of type 2 diabetes mellitus, multiple studies were conducted seeking to improve its hypoglycemic activity or to ameliorate aspects such as low oral absorption and the incidence of gastrointestinal side effects. Furthermore, efforts have been made to attribute new activities, or even to expand the pre-existing ones, that could enhance its effects on diabetes, such as pancreas-protective, antioxidant, and anti-inflammatory activities. In this paper, we describe the analogs of metformin developed in the last three decades, highlighting the lack of computationally based rational approaches to guide their development. We also discuss this is probably a consequence of how unclear the mechanism of action of the parent drug is and highlight the recent advances towards the establishment of the main molecular target(s) for metformin. We also explored the binding of metformin, buformin and phenformin to the mitochondrial respiratory chain complex I through molecular docking analyses and reviewed the prospects of applying computational tools to improve the success in the development of such analogs. Therefore, it becomes evident that the wide range of molecular targets and the multiple activities displayed by metformin make this drug a promising prototype for developing novel entities, particularly for treating type 2 diabetes mellitus.
Assuntos
Antimaláricos , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Açúcares , Simulação de Acoplamento Molecular , Antimaláricos/uso terapêuticoRESUMO
Aging is associated with glucose metabolism disturbances, such as insulin resistance and hyperinsulinemia, which contribute to the increased prevalence of type 2 diabetes (T2D) and its complications in the elderly population. In this sense, some bile acids have emerged as new therapeutic targets to treat TD2, as well as associated metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic acid (TUDCA) improves glucose homeostasis in T2D, obesity, and Alzheimer's disease mice model. However, its effects in aged mice have not been explored yet. Here, we evaluated the actions of TUDCA upon glucose-insulin homeostasis in aged C57BL/6 male mice (18-month-old) treated with 300 mg/kg of TUDCA or its vehicle. TUDCA attenuated hyperinsulinemia and improved glucose homeostasis in aged mice, by enhancing liver insulin-degrading enzyme (IDE) expression and insulin clearance. Furthermore, the improvement in glucose-insulin homeostasis in these mice was accompanied by a reduction in adiposity, associated with adipocyte hypertrophy, and lipids accumulation in the liver. TUDCA-treated aged mice also displayed increased energy expenditure and metabolic flexibility, as well as a better cognitive ability. Taken together, our data highlight TUDCA as an interesting target for the attenuation of age-related hyperinsulinemia and its deleterious effects on metabolism.
Assuntos
Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Idoso , Camundongos , Masculino , Humanos , Animais , Ácidos e Sais Biliares , Diabetes Mellitus Tipo 2/tratamento farmacológico , Camundongos Endogâmicos C57BL , Hiperinsulinismo/tratamento farmacológico , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Tauroquenodesoxicólico/uso terapêutico , Insulina/metabolismo , Obesidade/tratamento farmacológico , Glucose/metabolismoRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. While cognitive deficits remain the major manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in food intake, body weight and energy balance are also present, both in AD patients and animal models. In this sense, the tauroursodeoxycholic acid (TUDCA) has shown beneficial effects both in reducing the central and cognitive markers of AD, as well as in attenuating the metabolic disorders associated with it. We previously demonstrated that TUDCA improves glucose homeostasis and decreases the main AD neuromarkers in the streptozotocin-induced AD mouse model (Stz). Besides that, TUDCA-treated Stz mice showed lower body weight and adiposity. Here, we investigated the actions of TUDCA involved in the regulation of body weight and adiposity in Stz mice, since the effects of TUDCA in hypothalamic appetite control and energy homeostasis have not yet been explored in an AD mice model. The TUDCA-treated mice (Stz + TUDCA) displayed lower food intake, higher energy expenditure (EE) and respiratory quotient. In addition, we observed in the hypothalamus of the Stz + TUDCA mice reduced fluorescence and gene expression of inflammatory markers, as well as normalization of the orexigenic neuropeptides AgRP and NPY expression. Moreover, leptin-induced p-JAK2 and p-STAT3 signaling in the hypothalamus of Stz + TUDCA mice was improved, accompanied by reduced acute food intake after leptin stimulation. Taken together, we demonstrate that TUDCA treatment restores energy metabolism in Stz mice, a phenomenon that is associated with reduced food intake, increased EE and improved hypothalamic leptin signaling. These findings suggest treatment with TUDCA as a promising therapeutic intervention for the control of energy homeostasis in AD individuals.
Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Metabolismo Energético/efeitos dos fármacos , Homeostase , Estreptozocina/efeitos adversos , Ácido Tauroquenodesoxicólico/farmacologia , Adiposidade , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Animais , Biomarcadores , Peso Corporal , Gerenciamento Clínico , Modelos Animais de Doenças , Expressão Gênica , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Especificidade de Órgãos , Transdução de Sinais , TermogêneseRESUMO
The endoplasmic reticulum (ER) stress is one of the mechanisms related to decreased insulin secretion and beta cell death, contributing to the progress of type 2 diabetes mellitus (T2D). Thus, investigating agents that can influence this process would help prevent the development of T2D. Recently, the growth-hormone-releasing hormone (GHRH) action has been demonstrated in INS-1E cells, in which it increases cell proliferation and insulin secretion. As the effects of GHRH and its agonists have not been fully elucidated in the beta cell, we proposed to investigate them by evaluating the role of the GHRH agonist, MR-409, in cells under ER stress. Our results show that the agonist was unable to ameliorate or prevent ER stress. However, cells exposed to the agonist showed less oxidative stress and greater survival even under ER stress. The mechanisms by which GHRH agonist, MR-409, leads to these outcomes require further investigation.
Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Indóis/efeitos adversos , Células Secretoras de Insulina/citologia , Sermorelina/análogos & derivados , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Hormônio do Crescimento/agonistas , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Sermorelina/farmacologiaRESUMO
Bear bile has been used in Traditional Chinese Medicine for thousands of years due to its therapeutic potential and clinical applications. The tauroursodeoxycholic acid (TUDCA), one of the acids found in bear bile, is a hydrophilic bile acid and naturally produced in the liver by conjugation of taurine to ursodeoxycholic acid (UDCA). Several studies have shown that TUDCA has neuroprotective action in several models of neurodegenerative disorders (ND), including Alzheimer's disease, Parkinson's disease, and Huntington's disease, based on its potent ability to inhibit apoptosis, attenuate oxidative stress, and reduce endoplasmic reticulum stress in different experimental models of these illnesses. Our research extends the knowledge of the bile acid TUDCA actions in ND and the mechanisms and pathways involved in its cytoprotective effects on the brain, providing a novel perspective and opportunities for treatment of these diseases.
Assuntos
Doenças Neurodegenerativas/tratamento farmacológico , Ácido Tauroquenodesoxicólico/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa/métodos , Ácido Tauroquenodesoxicólico/metabolismo , Ácido Ursodesoxicólico/metabolismo , Ácido Ursodesoxicólico/farmacologiaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder and the major cause of dementia. According to predictions of the World Health Organization, more than 150 million people worldwide will suffer from dementia by 2050. An increasing number of studies have associated AD with type 2 diabetes mellitus (T2DM), since most of the features found in T2DM are also observed in AD, such as insulin resistance and glucose intolerance. In this sense, some bile acids have emerged as new therapeutic targets to treat AD and metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA), reduces amyloid oligomer accumulation and improves cognition in APP/PS1 mice model of AD, and also improves glucose-insulin homeostasis in obese and type 2 diabetic mice. Herein, we investigated the effect of TUDCA upon glucose metabolism in streptozotocin-induced AD mice model (Stz). The Stz mice that received 300 mg/kg TUDCA during 10 days (Stz + TUDCA), showed improvement in glucose tolerance and insulin sensitivity, reduced fasted and fed glycemia, increased islet mass and ß-cell area, as well as increased glucose-stimulated insulin secretion, compared with Stz mice that received only PBS. Stz + TUDCA mice also displayed lower neuroinflammation, reduced protein content of amyloid oligomer in the hippocampus, improved memory test and increased protein content of insulin receptor ß-subunit in the hippocampus. In conclusion, TUDCA treatment enhanced glucose homeostasis in the streptozotocin-induced Alzheimer's disease mice model, pointing this bile acid as a good strategy to counteract glucose homeostasis disturbance in AD pathology.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Ácidos e Sais Biliares/metabolismo , Glicemia/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ácido Tauroquenodesoxicólico/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Glucose/metabolismo , Glucose/farmacologia , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação/tratamento farmacológico , Insulina/sangue , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Testes de Memória e Aprendizagem , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Estreptozocina/toxicidade , Ácido Tauroquenodesoxicólico/administração & dosagemRESUMO
ARHGAP21 is a RhoGAP protein implicated in the modulation of insulin secretion and energy metabolism. ARHGAP21 transient-inhibition increase glucose-stimulated insulin secretion (GSIS) in neonatal islets; however, ARHGAP21 heterozygote mice have a reduced insulin secretion. These discrepancies are not totally understood, and it might be related to functional maturation of beta cells and peripheral sensitivity. Here, we investigated the real ARHGAP21 role in the insulin secretion process using an adult mouse model of acute ARHGAP21 inhibition, induced by antisense. After ARHGAP21 knockdown induction by antisense injection in 60-day old male mice, we investigated glucose and insulin tolerance test, glucose-induced insulin secretion, glucose-induced intracellular calcium dynamics, and gene expression. Our results showed that ARHGAP21 acts negatively in the GSIS of adult islet. This effect seems to be due to the modulation of important points of insulin secretion process, such as the energy metabolism (PGC1α), Ca2+ signalization (SYTVII), granule-extrusion (SNAP25), and cell-cell interaction (CX36). Therefore, based on these finds, ARHGAP21 may be an important target in Diabetes Mellitus (DM) treatment.
Assuntos
Proteínas Ativadoras de GTPase/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Hiperinsulinismo/prevenção & controle , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Animais , Homeostase , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Edulcorantes/farmacologiaRESUMO
As desordens psicológicas têm se ampliado neste século e acometem pessoas de diferentes idades e perfis socioeconômicos. Diante desse cenário, o presente trabalho busca debater e demonstrar como o lazer e a arteterapia podem ser alternativas para o tratamento de pessoas com depressão, além de auxiliares no controle do avanço dessa doença, por meio da conexão entre lazer, arte e saúde. Utilizou-se como metodologia as pesquisas bibliográfica e de campo com enfoque qualitativo, cujos dados evidenciaram a carência de trabalhos com o mesmo enfoque e apresentaram um panorama de como psicólogos e arteterapeutas de Belém-PA têm (ou não) utilizado o lazer e a arteterapia como auxiliares ao bem-estar do indivíduo e na prevenção de doenças.
Psychological disorders have expanded in this century and affect people of different ages and socioeconomic conditions. Given this scenario, the present study seeks to discuss and demonstrate how leisure and art therapy can be alternatives for the treatment of people with depression, in addition to helping to control the progress of this disease through the connection between leisure, art, and health. The methods used were bibliographic and field research with a qualitative approach, whose data showed the lack of similar works and showed an overview of how psychologists and art therapists in Belém-PA have (or not) used leisure and art therapy as aids to people's well-being and disease prevention.
Assuntos
Atividades de LazerRESUMO
O objetivo desta revisão sistemática é identificar a influência das redes sociais e tecnologias na retenção de clientes em ginásios. A pesquisa foi efetuada em quatro bases de dados online, de 2011 a 2019. Através do método PRISMA (MOHER et al., 2009), foram selecionados dez artigos. Os resultados evidenciaram que as redes sociais e o uso de tecnologias são fundamentais no processo de retenção. Após a análise dos dez artigos, foram também identificadas e analisadas as variáveis características pessoais dos sócios, frequência e tempo de utilização e qualidade do serviço e satisfação, como influenciadoras da retenção de clientes. Resumindo, este estudo fez uma revisão dos artigos que estudam o impacto das tecnologias e redes sociais na retenção de clientes em ginásios e ajudou a identificar outros fatores que incidem na retenção clientes, agrupando-os em duas dimensões, associadas à empresa e ao cliente.
The purpose of this systematic review is to identify the influence of social media and technologies on customer retention in gyms. The survey was conducted on four online databases from 2011 to 2019. Ten articles were selected through the PRISMA method (MOHER et al., 2009). The results showed that social media and the use of technologies are crucial in the retention process. After analyzing the ten articles, we also identified and analyzed the variables 'personal characteristic of members,' 'attendance and time of use,' 'quality of service and satisfaction' as influencing customer retention. In summary, this study reviewed the articles that study the impact of technologies and social networks on customer retention by gyms and helped to identify other factors that focus on retention, grouping them into two dimensions associated with the company and customers.
El objetivo de esta revisión sistemática es identificar la influencia de las redes sociales y las tecnologías en la retención de clientes en gimnasios. La investigación se llevó a cabo en cuatro bases de datos on-line, de 2011 a 2019. A través del método PRISMA (MOHER et al., 2009), se seleccionaron diez artículos. Los resultados mostraron que las redes sociales y el uso de tecnologías son fundamentales en el proceso de retención. Después de analizar los diez artículos, también se identificaron y analizaron las variables características personales de los socios, frecuencia y tiempo de uso, calidad del servicio y satisfacción, como elementos que influyen en la retención de clientes. En resumen, este estudio revisó los artículos que estudian el impacto de las tecnologías y las redes sociales en la retención de clientes en los gimnasios y ayudó a identificar otros factores que inciden en la retención de clientes, agrupándolos en dos dimensiones, empresa y cliente.
Assuntos
Humanos , Masculino , Feminino , Tecnologia , Academias de Ginástica , Rede Social , Satisfação Pessoal , Inquéritos e Questionários , Revisão , Mídias SociaisRESUMO
Coffee production is a global industry valued at approximately 173 billion US dollars. One of the main challenges facing coffee production is the management of the coffee berry borer (CBB), Hypothenemus hampei, which is considered the primary arthropod pest of coffee worldwide. Current control strategies are inefficient for CBB management. Although biotechnological alternatives, including RNA interference (RNAi), have been proposed in recent years to control insect pests, characterizing the genetics of the target pest is essential for the successful application of these emerging technologies. In this study, we employed RNA-seq to obtain the transcriptome of three developmental stages of the CBB (larva, female and male) to increase our understanding of the CBB life cycle in relation to molecular features. The CBB transcriptome was sequenced using Illumina Hiseq and assembled de novo. Differential gene expression analysis was performed across the developmental stages. The final assembly produced 29,434 unigenes, of which 4,664 transcripts were differentially expressed. Genes linked to crucial physiological functions, such as digestion and detoxification, were determined to be tightly regulated between the reproductive and nonreproductive stages of CBB. The data obtained in this study help to elucidate the critical roles that several genes play as regulatory elements in CBB development.
Assuntos
Coffea/parasitologia , Genes de Insetos , Gorgulhos/crescimento & desenvolvimento , Gorgulhos/genética , Animais , Feminino , Perfilação da Expressão Gênica , Larva/genética , Larva/crescimento & desenvolvimento , Masculino , RNA-Seq , TranscriptomaRESUMO
Susceptibility during fasting has been reported for the common vampire bat (Desmodus rotundus), to the point of untimely deaths after only 2-3 nights of fasting. To investigate the underlying physiology of this critical metabolic condition, we analyzed serum insulin levels, pancreatic islets morphometry and immunocytochemistry (ICC), static insulin secretion in pancreas fragments, and insulin signaling mechanism in male vampire bats. A glucose tolerance test (ipGTT) was also performed. Serum insulin was found to be lower in fed vampires compared to other mammals, and was significantly reduced after 24h fasting. Morphometrical analyses revealed small irregular pancreatic islets with reduced percentage of ß-cell mass compared to other bats. Static insulin secretion analysis showed that glucose-stimulated insulin secretion was impaired, as insulin levels did not reach significance under high glucose concentrations, whereas the response to the amino acid leucin was preserved. Results from ipGTT showed a failure on glucose clearance, indicating glucose intolerance due to diminished pancreatic insulin secretion and/or decreased ß-cell response to glucose. In conclusion, data presented here indicate lower insulinemia and impaired insulin secretion in D. rotundus, which is consistent with the limited ability to store body energy reserves, previously reported in these animals. Whether these metabolic and hormonal features are associated with their blood diet remains to be determined. The peculiar food sharing through blood regurgitation, reported to this species, might be an adaptive mechanism overcoming this metabolic susceptibility.
Assuntos
Quirópteros/metabolismo , Jejum , Intolerância à Glucose/veterinária , Insulina/metabolismo , Animais , Feminino , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose/veterinária , Imuno-Histoquímica , Insulina/sangue , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , MasculinoRESUMO
Respiratory syncytial virus (RSV) is the most common cause of severe respiratory infections worldwide, and an important cause of childhood bronchiolitis, pneumonia, and mortality. Although prevention of RSV infection by immunoprophylaxis with palivizumab has proved effective, a precise understanding of the timing of RSV outbreaks is necessary to ensure that infants are protected when RSV is circulating. In this study a consistent shift in the seasonal patterns of RSV circulation in southeast Brazil (São Paulo) is reported based on the analysis of 15 years of viral surveillance. Surveillance was conducted from 1996 to 2010 and involved the collection of samples from children with symptoms of acute respiratory infection. Putative changes in school terms, in the proportion of RSV genotypes infecting children and in the seasonal dynamics of several climatic parameters during the period were also investigated. The results revealed a progression in the timing of RSV seasons, with a shift in the onset and peak of RSV epidemics from 2007 onwards. Although lower rainfall and temperatures were associated with the onset of outbreaks, there was no evidence of changes in climate, school terms or in the relative proportion of genotypes in the period analyzed. These findings have direct implications for improving the prophylactic use of palivizumab, and stress the importance of fine tuning prophylaxis with recent surveillance data. In the case of São Paulo, palivizumab prophylaxis should be initiated earlier than suggested currently. Similar adjustments may be necessary in other regions.
Assuntos
Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Brasil/epidemiologia , Pré-Escolar , Humanos , Incidência , Lactente , Estações do Ano , Vigilância de Evento Sentinela , Temperatura , Tempo (Meteorologia)RESUMO
Trata-se de uma pesquisa experimental com a participação de voluntários de ambos os sexos com idade entre 18 e 60 anos. As amostras utilizadas neste estudo foram amostras de urina. Estas foram enviadas imediatamente ao laboratório de microbiologia, onde, sob condições ideais, foram submetidas a duas metodologias para conservação sob refrigeração denominadas, respectivamente, de Situação Temporal Dois (ST2) e Situação Temporal Três (ST3) e comparadas à Situação temporal Padrão, representada por uma análise imediata da amostra (ST1). Os resultados foram avaliados pelo teste de Wilcoxon, que evidenciou, em relação às situações ST1 e ST2, uma diferença significativa de apenas um parâmetro (hemácias), enquanto que, na comparação entre as situações ST1 e ST3, obteve-se alterações significativas em vários parâmetros como cristais, hemácias, células e aspecto. O estudo confirma que a refrigeração não é uma metodologia tão eficaz no que se refere à conservação de amostras para a realização da urinálise.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Controle de Qualidade , Refrigeração , Manejo de Espécimes , Estatísticas não Paramétricas , UrináliseRESUMO
Alterations in food intake such as caloric restriction modulate the expression of SIRT1 and SIRT4 proteins that are involved in pancreatic ß-cell function. Here, we search for a possible relationship between insulin secretion and the expression of SIRT1, SIRT4, PKC and PKA in islets from adult rats submitted to CR for 21 days. Rats were fed with an isocaloric diet (CTL) or received 60% (CR) of the food ingested by CTL. The dose-response curve of insulin secretion to glucose was shifted to the right in the CR compared with CTL islets (EC(50) of 15.1±0.17 and 10.5±0.11 mmol/L glucose). Insulin release by the depolarizing agents arginine and KCl was reduced in CR compared with CTL islets. Total islet insulin content and glucose oxidation were also reduced in CR islets. Leucine-stimulated secretion was similar in both groups, slightly reduced in CR islets stimulated by leucine plus glutamine but higher in CR islets stimulated by ketoisocaproate (KIC). Insulin secretion was also higher in CR islets stimulated by carbachol, compared with CTL islets. No differences in the rise of cytosolic Ca(2+) concentrations stimulated by either glucose or KCl were observed between groups of islets. Finally, SIRT1, but not SIRT4, protein expression was lower in CR compared with CTL islets, whereas no differences in the expression of PKC and PKA proteins were observed. In conclusion, the lower insulin secretion in islets from CR rats was, at least in part, due to an imbalance between the expression of SIRT1 and SIRT4.