127 research outputs found
Insulin and angiotensin II signaling pathways cross-talk:implications with the association between diabetes mellitus, arterial hypertension and cardiovascular disease
Mecanismos epidemiológicos e moleculares que associam obesidade e câncer
About 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. These results are alarming, as the world knows a pandemy of obesity and, in consequence, insulin resistance. Obesity may increase risk for various cancers by several mechanisms, including increasing sex and metabolic hormones, and inflammation. Here, we present a review of epidemiological and molecular evidences linking obesity and cancer - particularly colorectal, post-menopausal breast, endometrial, pancreatic, high grade prostate, hepatocellular, gallbladder, kidney and esophageal adenocarcinoma. The expected striking increase in the incidence of cancer in the near future related to obesity turns the knowledge of this field of great impact as it is needed to the development of strategies to prevent and treat this disease.Aproximadamente 25% dos casos de câncer são decorrentes do excesso de peso e do modo de vida sedentário. Esses resultados são alarmantes, pois o mundo vive uma pandemia de obesidade e, consequentemente, de resistência à insulina. A obesidade pode aumentar o risco de vários tipos de câncer por diversos mecanismos, incluindo aumento dos hormônios sexuais e metabólicos, e de inflamação. Neste trabalho, apresentamos uma revisão das evidências epidemiológicas e moleculares que relacionam a obesidade ao câncer - em particular aos cânceres colorretal, mamário na pós-menopausa, endometrial, pancreático, prostático avançado, hepatocelular, de bexiga, renal e esofágico. O aumento esperado da incidência de câncer relacionado à obesidade em um futuro próximo torna o conhecimento dessa área de grande importância, uma vez que este é fundamental para o desenvolvimento de estratégias preventivas e terapêuticas para a doença.21322
An Eye for Possibilities in the Development of Children with Cerebral Palsy: Neurobiology and Neuropsychology in a Cultural-Historical Dynamic Understanding
Taking children with Cerebral Palsy (CP) as an example, the article seeks an understanding ofchildren with disabilities that connects neuropsychological theories of neural development withthe situated cognition perspective and the child as an active participant in its social practices. Theearly brain lesion of CP is reconceptualised as a neurobiological constraint that exists in therelations between the neural, cognitive and social levels. Through a multi-method study of twochildren with CP, it is analysed how neurobiological constraints arise, evolve and sometimes areresolved through local matches between the child and its social practices. The result is discussedas support of a developmental science approach that includes processes at the social practice levelalong with knowledge of biological processes
Draft of Cheyenne & Arapahoe Report
https://digitalcommons.assumption.edu/mallet-manuscripts/1030/thumbnail.jp
EGFR Tyrosine Kinase Inhibitor (PD153035) Improves Glucose Tolerance and Insulin Action in High-Fat Diet–Fed Mice
High-Fat Diet Induces Apoptosis of Hypothalamic Neurons
Consumption of dietary fats is amongst the most important environmental factors leading to obesity. In rodents, the consumption of fat-rich diets blunts leptin and insulin anorexigenic signaling in the hypothalamus by a mechanism dependent on the in situ activation of inflammation. Since inflammatory signal transduction can lead to the activation of apoptotic signaling pathways, we evaluated the effect of high-fat feeding on the induction of apoptosis of hypothalamic cells. Here, we show that consumption of dietary fats induce apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. This effect is dependent upon diet composition, and not on caloric intake, since pair-feeding is not sufficient to reduce the expression of apoptotic markers. The presence of an intact TLR4 receptor, protects cells from further apoptotic signals. In diet-induced inflammation of the hypothalamus, TLR4 exerts a dual function, on one side activating pro-inflammatory pathways that play a central role in the development of resistance to leptin and insulin, and on the other side restraining further damage by controlling the apoptotic activity
Fyn Mediates Leptin Actions in the Thymus of Rodents
BACKGROUND:Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade. METHODOLOGY/PRINCIPAL FINDINGS:Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression. CONCLUSION/SIGNIFICANCE:Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue
Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice
Accumulating evidence has demonstrated that S-nitrosation of proteins plays a critical role in several human diseases. Here, we explored the role of inducible nitric oxide synthase (iNOS) in the S-nitrosation of proteins involved in the early steps of the insulin-signaling pathway and insulin resistance in the skeletal muscle of aged mice. Aging increased iNOS expression and S-nitrosation of major proteins involved in insulin signaling, thereby reducing insulin sensitivity in skeletal muscle. Conversely, aged iNOS-null mice were protected from S-nitrosation–induced insulin resistance. Moreover, pharmacological treatment with an iNOS inhibitor and acute exercise reduced iNOS-induced S-nitrosation and increased insulin sensitivity in the muscle of aged animals. These findings indicate that the insulin resistance observed in aged mice is mainly mediated through the S-nitrosation of the insulin-signaling pathway
Central Exercise Action Increases the AMPK and mTOR Response to Leptin
AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR) are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus
Hepatic and biochemical repercussions of a polyunsaturated fat-rich hypercaloric and hyperlipidic diet in Wistar rats
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