Abstract The hypothesis of this study was that the peri-implant bone healing of the group of pinealectomized rats would differ from the control group. The samples were subjected to immunohistochemical, microtomographic (total porosity and connectivity density), and fluorochrome (mineralized surface) analyses. Objectives The goal of this study was to investigate the cellular changes and bone remodeling dynamics along the bone/implant interface in pinealectomized rats. Material and Methods The total of 18 adult male rats (Rattus norvegicus albinus, Wistar) was divided into three groups (n=6): control (CO), pinealectomized without melatonin (PNX) and pinealectomized with melatonin (PNXm). All animals were submitted to the first surgery (pinealectomy), except the CO group. Thirty days after the pinealectomy without melatonin, the second surgery was conducted, in which all animals received an implant in each tibia (36 titanium implants with surface treatment were installed – Implalife® São Paulo, SP, Brazil). By gavage, the rats of the PNX group received the vehicle solution, and the procedure. Results Immunohistochemical analysis for runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OP) and osteocalcin (OC) showed that the bone repair process in the PNXm group was similar to that of the CO group, whereas the PNX group showed a delay. The microtomographic parameters of total porosity [Po(tot)] and bone surface (BS) showed no statistically significant differences, whereas for the connective density (Conn.Dn) a statistical difference was found between the CO and PNXm groups. Fluorochrome analysis of the active mineralized surface showed statistically significant difference between the CO and PNX and between the CO and PNXm groups. Conclusion The absence of the pineal gland impaired the bone repair process during osseointegration, however the daily melatonin replacement was able to restore this response.

Resumo A contagem de plaquetas está associada a doenças inflamatórias como a diabetes mellitus (DM), que, por sua vez, está relacionada de forma bidirecional com periodontite apical e com a doença periodontal. O objetivo deste estudo foi avaliar os efeitos da periodontite apical e/ou da doença periodontal na contagem de plaquetas utilizando o modelo de rato para DM. Oitenta ratos Wistar foram divididos aleatoriamente em 8 grupos (n=10): controle (C), periodontite apical (AP), doença periodontal (PD), periodontite apical com doença periodontal (AP-PD), diabetes mellitus (DM), diabetes mellitus com periodontite apical (DM-AP), diabetes mellitus com doença periodontal (DM-PD) e diabetes mellitus com periodontite apical e doença periodontal (DM-AP-PD). Os ratos foram anestesiados e a DM foi induzida com uma dose única de estreptozotocina diluída na solução tampão citrato. Após 6 dias, o DM foi confirmada. Os animais foram sedados e a periodontite apical foi induzida pela exposição dentária e a doença periodontal foi induzida por ligadura periodontal. Após 30 dias, os animais foram anestesiados e o sangue foi coletado por punção cardíaca. As amostras foram processadas e a contagem média de plaquetas foi obtida. Os dados foram tabulados e submetidos a análise estatística (p <0,05). Os ratos diabéticos apresentaram níveis glicêmicos médios mais elevados em comparação com ratos não diabéticos aos 6 e 36 dias após a indução da DM (p <0,05). Os grupos DM-PD e DM-PD-AP mostraram aumento da contagem média de plaquetas em comparação com os grupos controle e AP (p <0,05). A doença periodontal isolada ou associada à periodontite apical influencia na contagem de plaquetas em modelo de rato para diabetes mellitus.

Abstract Platelet count is associated with inflammatory diseases like diabetes mellitus (DM), which in turn, is related in a bidirectional manner with apical periodontitis and periodontal disease. The aim of this study was to evaluate the effects of apical periodontitis and/or periodontal disease on mean platelet count in a rat model of diabetes mellitus. Eighty Wistar rats were randomly divided into 8 groups (n=10): control (C), apical periodontitis (AP), periodontal disease (PD), apical periodontitis with periodontal disease (AP-PD), diabetes mellitus (DM), diabetes mellitus with apical periodontitis (DM-AP), diabetes mellitus with periodontal disease (DM-PD) and diabetes mellitus with apical periodontitis and periodontal disease (DM-AP-PD). Rats were anesthetized and DM was induced with a single dose of streptozotocin diluted in citrate buffer solution. After 6 days, the DM was confirmed. The animals were sedated and apical periodontitis was induced by dental exposure and periodontal disease was induced by periodontal ligature. After 30 days, animals were anesthetized and the blood was collected by cardiac puncture. Samples were processed and the mean platelet count was obtained. Data were tabulated and subjected to statistical analysis (p<0.05). Diabetic rats had higher mean glycemic levels compared with nondiabetic rats at 6 and 36 days after DM induction (p<0.05). The DM-PD and DM-PD-AP groups showed increased mean platelet count compared to control and AP groups (p<0.05). The periodontal disease alone or associated with apical periodontitis influence mean platelet count in a rat model of diabetes mellitus.

Resumo A gravidez é um período que envolve alterações metabólicas importantes que permitem a manutenção da saúde e desenvolvimento fetal e materno. Este estudo teve como objetivo avaliar a relação entre doença periodontal, resistência à insulina, concentração de cortisol salivar e nível de estresse percebido em gestantes. Trata-se de um estudo transversal. A amostra foi composta por 96 gestantes entre o quinto e sétimo mês, registradas em Unidades Básicas de Saúde do Sistema Único de Saúde. A condição periodontal foi avaliada após a obtenção do consentimento livre e esclarecido das participantes. As participantes foram divididas em três grupos: pacientes controle com condição periodontal saudável (CN; n=46), com gengivite (GI; n=26) e com periodontite (PI; n=24). As amostras salivares e sanguíneas foram coletadas para avaliação da concentração salivar de cortisol, glicemia, insulinemia e índice HOMA-IR. Foi aplicado um questionário validado para verificação dos níveis de estresse percebido. Grupo PI apresentou níveis significativamente mais elevados (p<0,05) de glicose no sangue (CN: 4,43±0,05; GI: 4,46±0,04; PI: 4,68±0,08), insulinemia (CN: 6,93±0,45; GI: 8,87±0,79; PI: 12,77±1,30), resistência à insulina (CN: 1,40±0,10; GI: 1,81±0,18; PI: 2,66±0,29) em comparação com os grupos CN e GI. Os níveis de estresse percebido foram maiores (p<0,05) nos grupos PI e GI quando comparados ao grupo CN (CN: 20,5±1,26; GI: 25,8±1,95; PI: 26,6±1,36). Não houve diferença significativa na concentração de cortisol salivar entre os grupos (CN: 11,13±0,58; GI: 11,96±0,74; PI: 11,47±0,74). Concluiu-se que há uma relação entre os níveis mais elevados de estresse percebido, resistência à insulina e ocorrência da doença periodontal durante a gravidez. Este estudo enfatiza a importância de prevenir a periodontite, a fim de evitar a resistência à insulina e estresse durante a gravidez, uma vez que estes podem causar complicações sistêmicas para a mãe e para o feto.

Abstract Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemy (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

Objectives Fluoride levels in the public water supplies of 40 Brazilian cities were analyzed and classified on the basis of risk/benefit balance. Material and Methods Samples were collected monthly over a seven-year period from three sites for each water supply source. The samples were analyzed in duplicate in the laboratory of the Center for Research in Public Health - UNESP using an ion analyzer coupled to a fluoride-specific electrode. Results A total of 19,533 samples were analyzed, of which 18,847 were artificially fluoridated and 686 were not artificially fluoridated. In samples from cities performing water fluoridation, 51.57% (n=9,720) had fluoride levels in the range of 0.55 to 0.84 mg F/L; 30.53% (n=5,754) were below 0.55 mg F/L and 17.90% (n=3,373) were above 0.84 mg F/L (maximum concentration=6.96 mg F/L). Most of the cities performing fluoridation that had a majority of samples with fluoride levels above the recommended parameter had deep wells and more than one source of water supply. There was some variability in the fluoride levels of samples from the same site and between collection sites in the same city. Conclusions The majority of samples from cities performing fluoridation had fluoride levels within the range that provides the best combination of risks and benefits, minimizing the risk of dental fluorosis while preventing dental caries. The conduction of studies about water distribution systems is suggested in cities with high natural fluoride concentrations in order to optimize the use of natural fluoride for fluoridation costs and avoid the risk of dental fluorosis.

This study evaluated the occurrence of highly or minimally leukotoxic strains of Aggregatibacter actinomycetemcomitans (Aa) from patients with Down syndrome and the distribution of the different serotype-specific genotypes of this microorganism. Sixty-seven patients with Down syndrome were subjected to dental, periodontal and radiographic evaluations. Samples of subgingival biofilm were collected and plated onto TSBV agar and characteristic colonies of A. actinomycetemcomitans were identified by biochemical methods. The occurrence of this bacterium was also evaluated directly in the clinical specimens by PCR. The presence of 530 bp deletion in the promoter region was also determined by PCR in order to evaluate distribution of highly or minimally leukotoxic strains. A. actinomycetemcomitans was detected in 11.1% by culture and 22.2% by PCR from periodontally healthy subjects, 100% of the patients with Down syndrome with aggressive periodontitis, 50% and 75% of patients with chronic periodontitis by culture and PCR respectively. Only two patients with aggressive periodontitis were colonized by highly leukotoxic Aa. Serotype-specific genotypes a and c were the most prevalent. The results suggest the role of peculiar characteristics of Aa and patients with Down syndrome in the development of periodontitis and the influence of peculiar characteristics of the population in this process.

Este estudio evaluó la presencia de cepas altamente o mínimamente toxicas de Aggregatibacter actinomycetemcomitans (Aa) de los pacientes con síndrome de Down y la distribución de los serotipos genotipos específicos de este microrganismo por cultivo y PCR. Sesenta y siete pacientes con síndrome de Down fueron sometidos a un tratamiento dental y evaluaciones clínicas. Las muestras de biofilme subgingival fueron recogidas y cultivadas en agar TSBV y colonias características de Aa fueran identificadas mediante métodos bioquímicos. La presencia de esta bacteria se evaluó también directamente en las muestras clínicas por PCR. Los aislados y las muestras clínicas también se probaron con el fin de evaluar la distribución de serotipos de genotipos específicos por PCR, mientras que la presencia de delección de 530 bp en la región promotora del gen ltxC también fue determinado por PCR con el fin de evaluar de distribución de las cepas altamente o mínimamente toxicas. Aa fue aislado en 11,1% y 22,2% por PCR de pacientes periodontalmente sanos; en todos los pacientes con síndrome de Down con periodontitis agresiva, y en 50% y 75% de los pacientes con periodontitis crónica por cultivo y PCR, respectivamente. Sólo dos pacientes con periodontitis agresiva fueron colonizados por cepas altamente tóxicas. Los serotipos y genotipos específicos a y c fueron los más frecuentes. Los resultados sugieren una asociación de las peculiares características de Aa con las características de los pacientes con síndrome de Down en el desarrollo de la periodontitis.

Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. Objectives: The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). Material and Methods: Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. Results: The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. Conclusions: These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats.

Reconhecida como um dos dez mais importantes avanços na Saúde Pública do século 20, a fluoretação das águas de abastecimento é uma medida de grande alcance populacional, eficaz no controle da cárie dentária. A cidade de Araçatuba, na região noroeste do estado de São Paulo, iniciou a fluoretação em 1972 e baseado na média da temperatura máxima anual, deve manter o teor de flúor entre 0,6 a 0,8 mgF/L. O objetivo deste estudo foi analisar mensalmente os teores de fluoretos nas águas de abastecimento público, no município de Araçatuba, durante 72 meses. Amostras de água foram coletadas mensalmente, em dias úteis, diretamente da rede de distribuição, nos pontos previamente estabelecidos e analisadas, em duplicata, de novembro de 2004 a outubro de 2010, no laboratório do Núcleo de Pesquisa em Saúde Coletiva do Programa de Pós-Graduação em Odontologia Preventiva e Social (NEPESCO) da Faculdade de Odontologia de Araçatuba/UNESP, utilizando-se um analisador de íons acoplado a um eletrodo específico para flúor. Do total das amostras (n=591), 67,2% (n=397) apresentaram teores de flúor entre 0,6 e 0,8 mgF/L; 20,6% (n=122) abaixo de 0,6 mgF/L; 11,5% (n=68) entre 0,8 e 1,2 mgF/L e 0,7% (n=4) acima de 1,2 mgF/L. A maioria das amostras apresentou teores de fluoreto dentro dos parâmetros recomendados. Observou-se variação mínima entre os pontos de coleta analisados, demonstrando que o município tem obtido êxito no controle dos níveis de flúor presentes na água e evidenciando a importância da vigilância e monitoramento constantes para garantir a qualidade da água fornecida à população

Known as one of the ten most important advances on Public Health in the 20th century, fluoridation of public water supply is a measure of wide population coverage, which is effective on caries control. The city of Araçatuba, in the Northwest region of the São Paulo state, Brazil, started public water supply fluoridation in 1972 and, based on the average annual highest temperature, has kept the fluoride concentration between 0.6 to 0.8 mgF/L. The purpose of this study was to analyze monthly the fluoride concentration in public water supply in the city of Araçatuba during 72 months. Water samples were collected monthly on weekdays, directly from the water distribution network, on pre-established locations and analyzed in duplicate between November 2004 and October 2010 at the Research Laboratory of the Nucleus for Public Health (NEPESCO) of the Public Health Graduate Program from Araçatuba Dental School/UNESP, Brazil, using an fluoride-specific electrode connected to an ion analyzer. From the total of samples (n=591), 67.2% (n=397) presented fluoride concentration between 0.6 and 0.8 mgF/L; 20.6% (n=122) below 0.6 mgF/L; 11.5% (n=68) between 0.8 and 1.2 mgF/L and 0.7% (n=4) above 1.2 mgF/L. Most samples showed fluoride levels within the recommended parameters. Minimal variation was observed among the analyzed collection locations, showing that the city has been able to control the fluoride levels in the public water supply and reinforcing the importance of surveillance and constant monitoring to assure the quality of the water delivered to the population.

Este estudo relata a percepção de cuidadores de idosos que atuam em três instituições de amparo ao idoso na cidade de Araçatuba, São Paulo. Foram abordadas questões em relação ao envelhecimento, motivações pessoais dos cuidadores em buscar trabalho com essa parcela da população, relacionamento com o idoso, dificuldades durante o trabalho e a satisfação encontrada junto ao idoso. Realizou-se entrevista com os cuidadores, e o material verbal coletado foi analisado utilizando a técnica do Discurso do Sujeito Coletivo. Pôde-se perceber, através dos relatos, o envolvimento emocional do cuidador com seu trabalho, a sobrecarga física e emocional à qual está exposto. Relatos a respeito do envelhecimento também puderam ser coletados, além de questões de ordem social, que motivaram o cuidador a buscar esse tipo de trabalho. Os diversos olhares do cuidador nos impulsionam na busca de estratégias de capacitação teórica e suporte psicológico a esse grupo, pensando no seu bem-estar e no bem-estar do idoso.

This study reports elderly caregivers' perception in charge of giving assistance to three benefiting institutions in elderly care, in the city of Araçatuba, São Paulo, Brazil. Questions were approached regarding aging, caregivers' personal motivation in the search of working with this sector of population, relationship with elderly, most common difficulties found during work and caregivers' satisfaction. An interview was done with caregivers and the collected verbal material was analyzed through the Collective Subject Discursive Technique. It was possible to realize through the reports the emotional involvement of caregivers with their work as well as the emotional and physical overload which they are exposed to. Reports related to aging could also be collected as well as social questions which motivated caregivers to search for this kind of job. The several eyes of caregivers lead us to search for new strategies of theoretical capability and psychological support for this group, thinking of their well-being along with the elderly well-being.

Este estudo relata a percepção de cuidadores de idosos que atuam em três instituições de amparo ao idoso na cidade de Araçatuba, São Paulo. Foram abordadas questões em relação ao envelhecimento, motivações pessoais dos cuidadores em buscar trabalho com essa parcela da população, relacionamento com o idoso, dificuldades durante o trabalho e a satisfação encontrada junto ao idoso. Realizou-se entrevista com os cuidadores, e o material verbal coletado foi analisado utilizando a técnica do Discurso do Sujeito Coletivo. Pôde-se perceber, através dos relatos, o envolvimento emocional do cuidador com seu trabalho, a sobrecarga física e emocional à qual está exposto. Relatos a respeito do envelhecimento também puderam ser coletados, além de questões de ordem social, que motivaram o cuidador a buscar esse tipo de trabalho. Os diversos olhares do cuidador nos impulsionam na busca de estratégias de capacitação teórica e suporte psicológico a esse grupo, pensando no seu bem-estar e no bem-estar do idoso.

This study reports elderly caregivers' perception in charge of giving assistance to three benefiting institutions in elderly care, in the city of Araçatuba, São Paulo, Brazil. Questions were approached regarding aging, caregivers' personal motivation in the search of working with this sector of population, relationship with elderly, most common difficulties found during work and caregivers' satisfaction. An interview was done with caregivers and the collected verbal material was analyzed through the Collective Subject Discursive Technique. It was possible to realize through the reports the emotional involvement of caregivers with their work as well as the emotional and physical overload which they are exposed to. Reports related to aging could also be collected as well as social questions which motivated caregivers to search for this kind of job. The several eyes of caregivers lead us to search for new strategies of theoretical capability and psychological support for this group, thinking of their well-being along with the elderly well-being.

Estimativas de la Organización Mundial de Salud apuntan que el 10% de la población mundial de países desarrollados poseen algún tipo de deficiencia. En Brasil, ese porcentaje aumenta para el 14,5% de la población, y la sordera ocupa la tercera posición en prevalencia. Este estudio tiene el objetivo de analizar la percepción del deficiente auditivo cuanto al tratamiento personal recibido en consultorio odontológico. Fueron entrevistadas 27 personas sordas, que participaban del 6º Congreso Internacional de Sordos "Keirai Heiguiai", en la ciudad de Curitiba, Brasil. A éstos, se les entregó un formulario conteniendo cuestiones que trataban sobre el perfil del paciente, formas (métodos) de comunicación durante el atendimiento odontológico, percepción del tratamiento clínico y personal ofrecido por el cirujano oral. Cuanto a la escolaridad, 37,05% de los entrevistados posee el nivel de enseñanza media incompleta. El 46,15% de los 26 pacientes afirmaron haber sufrido discriminación. 92,31% relató haber sido bien atendida por el equipo de profesionales, sin embargo sólo el 30,77% afirmaron haber sido comprendidos por el dentista. A pesar de pequeña, hubo una diferencia en relación al porcentaje de los pacientes que no comprendió al dentista (30,77%) en relación a los que no fueron por él comprendidos (34,62%). El método más utilizado para la comunicación fue la ayuda de un intérprete (46,15%). Podemos concluir que el atendimiento odontológico y la relación profesional-paciente deben perfeccionarse para garantizar la satisfacción del paciente sordo y mejorar su salud y higiene bucal.

World Health Organization estimates that 10% of the world population in less developed countries has some physical deficiency. In Brazil, this percentage increases up to 14,5% in the total of population, and deafness occupies the third position in prevalence of deficiencies. This study aimed to analyze the perception of deaf in relation to the personal treatment received in dentist offices. An interview was carried out to 26 deaf persons that were participating in the 6th Deaf International Congress "Keirai Heiguiai" in the city of Curitiba, Brazil. A form containing questions on the profile of the patient, communication methods used during dental attendance and perception of the clinical and personal treatment given by the dentist was applied to 26 deaf. In relation to educational level, 37.05% of the interviewees had uncompleted medium level of education. 46.15% of the 26 patients stated that they had been discriminated during dental attendance. 92.31% related a good attendance by the dental staff, however only 30.77% mentioned that they had been well-understood by the dentist. There was a little difference between the percentages of patients who did not understand the dentist communication (30.77%) in relation to those who were not well-understood by the professionals (34.62%). The most used method of communication was the one supported by an interpreter (46.15%). We can conclude that the dental attendance as well as the patient-professional relation should be improved to guarantee satisfaction of the deaf and to enhance the oral health of these patients.

A influência da glândula pineal sobre o metabolismo de carboidratos vem sendo investigada há décadas. Entretanto, resultados contraditórios não esclarecem, até o momento, o verdadeiro papel da melatonina sobre a homeostasia dos carboidratos. Através de estudos recentes, contribuímos de maneira ineqüívoca para a caracterização do papel da glândula pineal como moduladora do metabolismo de carboidratos. Além disso, à luz dos conhecimentos atuais, demonstramos quais passos do mecanismo de ação da insulina estão envolvidos nessa modulação. Nossos estudos revelaram que a pinealectomia promove um quadro de resistência à insulina, sem obesidade. A captação máxima de 2-deoxi-glicose, estimulada por insulina, em adipócitos isolados está diminuída, sem entretanto modificar a capacidade da insulina ligar-se ao seu receptor e estimular a fosforilação dos substratos intracelulares representados pela pp 185. Por outro lado, em vários tecidos sensíveis à insulina, observou-se uma diminuição no conteúdo da proteína transportadora de glicose GLUT4, mas diminuição no mRNA do GLUT4 apenas em alguns desses tecidos, sugerindo uma regulação tecido-específica. Adicionalmente, foi demonstrado que a regulação da glândula pineal sobre o metabolismo de carboidratos é mediado pela melatonina: o hormônio aumentou a sensibilidade à insulina de adipócitos isolados e o tratamento de reposição com melatonina restaurou o conteúdo de GLUT4 no tecido adiposo branco. Em síntese, os estudos aqui relatados evidenciam um importante papel da glândula pineal na modulação da homeostasia de carboidratos. Essa regulação é dependente da melatonina e pode ser resumida, até o presente momento, como um aumento da sensibilidade tecidual à insulina, que envolve alterações na expressão gênica do GLUT4.

For decades, the influence of the pineal gland on carbohydrate metabolism has been investigated. However, contradictory results have not yet elucidated the role played by melatonin in carbohydrate homeostasis. In our recent studies, we have contributed to characterize the role of the pineal gland as a modulator of carbohydrate metabolism. In addition, based on present-day knowledge, we have demonstrated the steps of insulin action mechanism involved in this modulation. Our studies reveal that pinealectomy causes a condition of obesity-free insulin resistance. The maximum uptake of 2-deoxi-glucose prompted by insulin in isolated adipocytes is diminished, without however changing the insulin capacity to bind to its receptor, and to stimulate the phosphorilation of intracellular substrates represented by pp 185. Conversely, in several insulin-sensitive tissues, our studies detected a decrease in the amount of glucose transporter protein GLUT4, and a decrease in GLUT4 mRNA in only some of these tissues, suggesting a tissue-specific regulation. Additionally, it was demonstrated that the pineal gland regulation influences carbohydrate metabolism through melatonin, by our demonstration that the hormone increased insulin sensitivity of isolated adipocytes, and that melatonin replacement therapy restored the amount of GLUT4 in white adipose tissue. In summary, the studies reported here evidence an important role played by the pineal gland in the modulation of carbohydrate homeostasis. This regulation seems to be melatonin-dependent and can be described, so far, as an increase in tissue sensitivity to insulin, which involves changes in GLUT4 gene expression.

A resistência à insulina é um elemento chave na gênese de várias alterações fisiopatológicas. O esquema de restrição alimentar meal-feeding (MF) consiste na oferta de uma única refeição diária de 2h, sem, contudo, limitar a quantidade de alimento durante esse período. Este esquema determina várias adaptações morfo-metabólicas, algumas sugerindo maior sensibilidade à insulina. No presente estudo investigou-se, em adipócitos isolados, a sensibilidade à insulina de ratos submetidos a treinamento alimentar e tornados diabéticos (MFD) comparando-os com ratos em livre curso alimentar diabéticos (FFD). A curva dose resposta da captação de 2-deoxi-D-glicose estimulada por insulina sugeriu maior sensibilidade, enquanto a captação máxima foi significativamente maior (p<0,05) nos ratos MFD. Esta maior responsividade à insulina refletiu-se no metabolismo dos adipócitos que mostraram aumento (p<0,05) na capacidade máxima de oxidar glicose a CO2 e incorporar glicose em triacilglicerol. O aumento da resposta celular à insulina em ratos MFD refletiu-se in vivo em menor (p<0,05) insulinemia e maior (p<0,05) índice glicose/insulina (G/I). Em conjunto, os resultados indicam que o treinamento alimentar melhora a resposta à insulina em ratos diabéticos, o que pode representar uma abordagem alternativa no tratamento do diabetes mellitus.

Insulin resistance is a key element in the genesis of several pathophysiological changes. Meal feeding (MF) - one daily 2-hour meal, without food restriction in the period - determines several morpho-metabolic adaptations, some of them suggesting enhanced insulin sensitivity. In the present study with isolated adipocytes, we investigated insulin resistance in rats submitted to meal feeding, making them diabetic (MFD). Later, they were compared with diabetic rats under a free feeding diet (FFD). The insulin-stimulated 2-deoxy-D-glucose uptake dose-response curve suggested higher sensitivity, whereas maximum uptake was significantly higher (p<0.05) in MFD rats. This higher sensitivity to insulin had an impact on adipocyte metabolism which showed an increase (p<0.05) in its capacity to oxidize glucose to CO2 and to transform glucose into triacilglicerol. The increase in the cellular response to insulin in MFD rats in vivo resulted in lower insulinemia (p<0.05) and in higher glucose/insulin (G/I) index (p<0.05). In combination, these results indicate that meal feeding improves insulin response in diabetic rats, which can represent an alternative approach in treating diabetes mellitus.