Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats.

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.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats.

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκß) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation.

The regulation of Rasd1 expression by glucocorticoids and prolactin controls peripartum maternal insulin secretion.

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.

Quercetin decreases inflammatory response and increases insulin action in skeletal muscle of ob/ob mice and in L6 myotubes.

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.

Fructose-induced hypothalamic AMPK activation stimulates hepatic PEPCK and gluconeogenesis due to increased corticosterone levels.

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.

Ocorrência de dor na coluna vertebral e sua relação com a qualidade de vida de manicures e pedicures / Occurrence of spinal column pain and its relation to the quality of life of manicures and pedicures / Ocurrencia de dolor de espalda y su relación con la calidad de vida de manicuras y pedicuras

Analisar em manicures e pedicures a ocorrência de dor na coluna vertebral e verificar sua relação com a qualidade de vida. Métodos: Realizou-se, no período de fevereiro a junho de 2010, uma pesquisa quantitativa, do tipo transversal e descritiva, envolvendo 30 profissionais entre 18 e 45 anos com, no mínimo, um ano de profissão. Após seleção, aplicaram-se dois questionários: o SF-36 e outro, elaborado pelas pesquisadoras, com questões referentes à atividade ocupacional (jornada e tempo de serviço), presença de dor e suas características (local, tipo, frequência e intensidade). Resultados: Das 30 participantes, 76,7% (n=23) relataram dor, sendo 63,3% (n=19) na coluna lombar e 46,7% (n=14) do tipo crônica (com duração há mais de 6 meses). Relatou-se frequência de dor diária em 36,7% (n=11), com média de intensidade de 6,1±2,24. A idade e o tempo de serviço apresentaram-se maior no grupo com dor, com 34,2±6,80 e 12,3±6,39 anos, respectivamente. Na qualidade de vida do grupo sem dor, os domínios ?capacidade funcional?, ?dor? e ?estado geral de saúde? obtiveram maiores pontuações em relação ao grupo com dor (p<0,05). Conclusão: Detectou-se elevada presença de dor na coluna vertebral das manicures e pedicures avaliadas, principalmente na região lombar, levando a limitações funcionais e, consequentemente, ao comprometimento na qualidade de vida...

To analyze the occurrence of spine column pain in manicures/pedicures and verify its relationship with quality of life. Methods: A quantitative and descriptive crosssectional research conducted from February to June 2010 with 30 professionals aged between 18 and 45 years and with at least one year of work experience. After selection, two questionnaires were applied: the SF-36 and another developed by the researchers with questions related to occupation (working hours and length of service), occurrence of pain and its characteristics (location, type, frequency and intensity). Results: Of the 30 participants, 76.7% (n=23) reported pain, with 63.3% (n=19) occurrence in the lumbar spine and 46.7% (n=14) occurrence of chronic type (lasting more than 6 months). A total of 36.7% (n=11) of interviewees reported daily pain with an average intensity of 6.1+2.24. Age and length of service rates were higher in the group of people who felt pain (34.2+6.80 and 12.3+6.39 years respectively). Regarding the quality of life in the group of people who did not feel pain, the domains ?functional capacity?, ?pain? and ?general health status? had higher scores when compared to the group of people who felt pain (p<0.05). Conclusion: It was detected a high occurrence of spinal column pain among manicures / pedicures, especially in the lumbar spine, leading to functional limitations, and a consequent change in quality of life...

Analizar la ocurrencia de dolor de espalda en manicuras y pedicuras y verificar su relación con la calidad de vida. Métodos: Una investigación cualitativa se realizó en el período entre febrero y junio de 2010, del tipo trasversal y descriptiva involucrando 30 profesionales entre los 18 y 45 años con un mínimo de un año de profesión. Después de la selección fueron aplicados dos cuestionarios: el SF-36 y otro elaborado por las investigadoras con preguntas sobre la actividad ocupacional (jornada y tiempo de servicio), presencia de dolor y sus características (local, tipo, frecuencia e intensidad). Resultados: De las 30 participantes, el 76,7% (n=23) relataron dolor, siendo el 63,3% (n=19) en La lumbar y el 46,7% (n=14) del tipo crónica (con duración de más de seis meses). Se relató la frecuencia de dolor diaria enel 36,7% (n=11) con media de intensidad de 6,1±2,24. La edad y el tiempo de servicio se presentaron mayores en el grupo com dolor con 34,2±6,80 e 12,3±6,39 años, respectivamente. Respecto la calidad de vida del grupo sin dolor, los dominios ?capacidad funcional?, ?dolor? y ?estado general de salud? obtuvieron mayores puntuaciones en relación al grupo con dolor (p<0,05). Conclusión: Se detectó elevada presencia de dolor de espalda de las manicuras y pedicuras evaluadas, principalmente en La lumbar, llevando a limitaciones funcionales y, en consecuencia, AL comprometimiento de la calidad de vida...

Perfil funcional de pacientes com disfunção temporomandibular em tratamento fisioterápico / Functional profile of patients with temporomandibular joint dysfunction under physiotherapy treatment

Objetivos: Analisar o perfil funcional dos pacientes com disfunção temporomandibular (DTM) em tratamento fisioterápico. Métodos: Estudo transversal conduzido com 21 pacientes em atendimento fisioterápico durante o ano de 2007, no Núcleo de Atenção Médica Integrada (NAMI), Fortaleza CE, Brasil. Estes submeteram-se à anamnese (idade, presença de dor, locais acometidos e hábitos para funcionais) e avaliação funcional (presença de pontos gatilhos, amplitude de movimento e avaliação postural). Resultados: A idade variou de 16 a 56 anos, com média de 31,3 ± 14,85 e maior acometimento do sexo feminino, com 17 (81,0%) pacientes. Dos avaliados, 13 (61,9%) apresentavam intensidade de dor moderada, com média de 5,4 ± 0,50. Os locais de dor mais referidos eram a articulação temporomandibular (ATM) por 15 (71,4%) e a região cervical por 13 (61,9%) pacientes. Constatou-se que 13 (61,9%) avaliados relataram o apertamento como hábito parafuncional. Encontrou-se limitação significativa na abertura de boca e dos movimentos da região cervical quando comparado com os valores normais (p < 0,05). Os músculos mais dolorosos à palpação foram trapézio superior (n=19), pterigóide medial (n=15) e masseter (n=15). ATM apresentou-se com dor forte (grau 3) na palpação em 3 (14,3%) pacientes. Na avaliação postural, 10 (47,6%) tinham hiperlordose cervical, 7 (33%) apresentavam cabeça anteriorizada e 7 (33%) com ombros elevados. Conclusão: Os pacientes com DTM em tratamento fisioterápico apresentaramlimitação de movimento da ATM e cervical, dor, presença de pontos gatilhos e alterações posturais em estágio mais comprometido e sintomático dessa disfunção. Diante disso, tornase necessário prover avaliação e tratamento fisioterápicos precoces.

Objectives: To assess the functional profile of patients with temporomandibular joint dysfunction (TMJD) receiving physical therapy. Methods: A cross-sectional study carried with 21 patients receiving physiotherapy care during the year of 2007 at the Center for Integrated Medical Care (Núcleo de Atenção Médica Integrada - NAMI), in Fortaleza-CE, Brazil. Those were submitted to anamnesis (age, presence of pain, affected sites and parafunctional habits) and functional assessment (presence of trigger points, movement amplitude and postural evaluation). Results: The age varied from 16 to 56 years, with an average of 31.3 ± 14.85 and female gender was the most affected with 17 (81.0%) patients. Of the assessed patients, 13 (61.9%) presented pain of moderate intensity, with an average of 5.4 ± 0.50. The most common sites of pain were the temporomandibular joint (TMJ), reported by 15 (71.4%), and cervical region, reported by 13 (61.9%) patients. We found that 13 (61.9%) assessed patients reported clenching as parafunctional habit. Significant limitation of mouth opening and movements of the cervical region were observed when compared to normal values (p <0.05). The most painful muscles on palpation were upper trapezius (n=19), medial pterygoid (n=15) and the masseter (n=15). The TMJ presented strong pain (degree 3) on palpation in 3 (14.3%) patients. In postural assessment, 10 (47.6%) had cervical hyperlordosis, 7 (33%) had forward head posture and 7 (33%) had raised shoulders. Conclusion: Patients with TMJD receiving physical therapy present limitations in TMJ and cervical movement, pain, presence of trigger points and postural changes at a more compromised and symptomatic stage of this dysfunction. In view of this, it becomes necessary to provide early evaluationand treatment with physical therapy.