Incrétines, secretion d'insuline et diabète

Nutrient ingestion triggers a complex hormonal response aimed at stimulating glucose utilization in liver, muscle and adipose tissue to minimize the raise in blood glucose levels. Insulin secretion by pancreatic beta cells plays a major role in this response. Although the beta cell secretary response is mainly controlled by blood glucose levels, gut hormones secreted in response to food intake have an important role in potentiating glucose-stimulated insulin secretion. These gluco-incretin hormones are GLP-1 (glucagon-like peptide-1) and GIP (gluco-dependent insulinotropic polypeptide). Their action on pancreatic beta cells depends on binding to specific G-coupled receptors linked to activation of the adenylyl cyclase pathway. In addition to their effect on insulin secretion both hormones also stimulate insulin production at the transcriptional and translational level and positively regulate beta cell mass. Because the glucose-dependent insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide is now developed as a novel therapeutic drug for this disease.

A role for the endocrine and pro-inflammatory mediator MIF in the control of insulin secretion during stress.

The systemic response to injury or infection is often accompanied by significant alterations in host metabolism and glucose homeostasis. Within the liver, these changes include a decrease in glycogenesis and an increase in gluconeogenesis, and in peripheral tissues, the development of insulin resistance and the increased utilization of glucose by non-insulin-dependent pathways. Depending on the severity and the duration of the response, both hyper- and hypoglycemia can ensue and each can become a clinically important manifestation of the systemic inflammatory response. The protein known as macrophage migration inhibitory factor (MIF) has been identified recently to play a central role in host immunity and to regulate glucocorticoid effects on the immune and inflammatory systems. MIF is released in vivo from activated immune cells as well as by the anterior pituitary gland upon stimulation of the hypothalamic-pituitary-adrenal axis. MIF also has been found to be secreted together with insulin from the pancreatic beta-cells and to act as an autocrine factor to stimulate insulin release. Since circulating MIF levels are elevated during stress or systemic inflammatory processes, this protein may play a central role in the control of insulin secretion during various disease states.

Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis: improvement of engraftment following transplantation.

Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2-3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.

O turismo e a percepção dos seus impactes pela comunidade local : o caso da Ilha do Sal, Cabo Verde

The traditional analysis of tourism, having in mind only its economic impacts has been shown to be reductive and insufficient to explain the numerous and versatile modifications these can and will stimulate in a society at many levels, e.g. socially, culturally, politically and in the environment. The complexity of touristic activities and the insufficient measuring instruments that can provide exact data about these, gives terrain to the emergence of myths and value judgments around the effects in countries where tourism is a reality. This study aims at understanding how the impacts of tourism are grasped by the local community in Sal island – Cape Verde – convinced as we are that a quality and sustainable touristic offer can only be done by trialing the population, and involving them in the planning, managing and monitoring processes. The analysis of the perception of the impacts of touristic activities by the population tells us a lot about the levels of satisfaction of such communities towards the way in which the touristic development has been carried out in their surroundings. This study has been made through the inquiry of 231 locals, by means of a questionnaire, that showed that the population in this island has a very clear conscience of the impacts of tourism in their day-to-day lives. Conclusions drawn are that the negative economic and social impacts are greater than the positive; the cultural and environmental impacts are not so significant, and that the people feel that their voice has not been heard in what planning touristic activities is concerned. Nevertheless, they have high expectations regarding tourism as a way of ameliorating their life conditions. The inexistence of a linear behavior of impacts of touristic activities in the receptive countries and a perfect and adjustable model for tourism development make these countries delineate new politics aiming at the sustainability and the creation of conditions that help them monitor and mitigate its negative impacts.

O turismo e a percepção dos seus impactes pela comunidade local: o caso da Ilha do Sal, Cabo Verde

A análise tradicional do turismo visando apenas a sua dimensão económica tem-se mostrado redutora e insuficiente para explicar as inúmeras e versáteis alterações que pode provocar a nível social, cultural, político e ambiental. A complexidade da actividade turística e a carência de instrumentos ajustados para avaliar e tornar mensuráveis os seus impactes constituem terreno fértil à emergência de mitos e de juízos de valor em torno dos efeitos por ele causado nos países receptores. A linha orientadora da investigação parte do pressuposto que a actividade turística só faz sentido e se torna viável se proporcionar uma experiência qualitativa aos principais agentes envolvidos: os turistas e os residentes. A tentativa de compreender a forma como os impactes do turismo são percepcionados pela comunidade receptora da ilha do Sal em Cabo Verde está intimamente associado à convicção que um turismo de qualidade e sustentável só é possível auscultando a população e envolvendo-a no planeamento, gestão e monitorização da actividade. A análise da percepção dos impactes da actividade turística por parte da comunidade desemboca indirectamente no conhecimento dos níveis de satisfação da comunidade em relação à forma como se tem realizado o desenvolvimento turístico na ilha. No âmbito do trabalho de investigação foram realizados duzentos e trinta e um questionários cujos resultados da investigação levam a acreditar que a comunidade local salense possui uma clara consciência dos impactes do turismo no seu quotidiano. Verifica-se que a percepção dos impactes económicos e sociais negativos reúnem maior consenso que os impactes positivos. Os impactes culturais e ambientais são ainda pouco perceptíveis por parte dos inquiridos. Por outro lado, os inquiridos na sua generalidade não se sentem envolvidos no planeamento da actividade turística, embora haja elevadas expectativas em relação à actividade como forma de melhoria das condições de vida da população. A inexistência de um comportamento linear dos impactes da actividade turística no destino e de um modelo de desenvolvimento turístico perfeito e ajustável a todas as realidades obriga a que sejam delineados por parte dos países receptores políticas de planeamento visando a sustentabilidade e condições para a monitorização e mitigação dos seus impactes.

O turismo e a percepção dos seus impactes pela comunidade local : o caso da Ilha do Sal, Cabo Verde

The traditional analysis of tourism, having in mind only its economic impacts has been shown to be reductive and insufficient to explain the numerous and versatile modifications these can and will stimulate in a society at many levels, e.g. socially, culturally, politically and in the environment. The complexity of touristic activities and the insufficient measuring instruments that can provide exact data about these, gives terrain to the emergence of myths and value judgments around the effects in countries where tourism is a reality. This study aims at understanding how the impacts of tourism are grasped by the local community in Sal island – Cape Verde – convinced as we are that a quality and sustainable touristic offer can only be done by trialing the population, and involving them in the planning, managing and monitoring processes. The analysis of the perception of the impacts of touristic activities by the population tells us a lot about the levels of satisfaction of such communities towards the way in which the touristic development has been carried out in their surroundings. This study has been made through the inquiry of 231 locals, by means of a questionnaire, that showed that the population in this island has a very clear conscience of the impacts of tourism in their day-to-day lives. Conclusions drawn are that the negative economic and social impacts are greater than the positive; the cultural and environmental impacts are not so significant, and that the people feel that their voice has not been heard in what planning touristic activities is concerned. Nevertheless, they have high expectations regarding tourism as a way of ameliorating their life conditions. The inexistence of a linear behavior of impacts of touristic activities in the receptive countries and a perfect and adjustable model for tourism development make these countries delineate new politics aiming at the sustainability and the creation of conditions that help them monitor and mitigate its negative impacts.

Optimal magnitude and probability of fines

The economic literature on crime and punishment focuses on the trade-off between probability and severity of punishment, and suggests that detection probability and fines are substitutes. In this paper it is shown that, in presence of substantial underdeterrence caused by costly detection and punishment, these instruments may become complements. When offenders are poor, the deterrent value of monetary sanctions is low. Thus, the government does not invest a lot in detection. If offenders are rich, however, the deterrent value of monetary sanctions is high, so it is more profitable to prosecute them.

A Importância da Diáspora na Política Externa de Cabo Verde

Com a globalização, a emigração tem-se tornado cada vez mais um assunto que desperta muito interesse, por parte dos estudiosos. A emigração tem ganhado um forte cunho nas Relações Internacionais, já que com a alteração do Sistema internacional, o Estado deixou de ser o único actor da cena internacional. Por isso desperta muito o interesse em aprofundar os estudos sobre a emigração que é um fenómeno que tem acontecido no sistema internacional há várias décadas. Após a segunda guerra mundial e com a globalização tem-se verificado muita emigração de sul para norte, em busca de melhores condições de vida. Hoje em dia é comum quando se fala da emigração falar-se da diáspora que é um termo usado para designar a dispersão dos Judeus “exilados/expulsos” da sua terra de origem Palestina. Mas vários investigadores têm usado este termo para caracterizar a emigração cabo-verdiana para várias partes do mundo. E sem fugir à regra, Cabo Verde é um exemplo de fuga de sul para norte. Os cabo-verdianos emigram para norte à procura de melhores condições de vida. E hoje, já não se fala nos emigrantes cabo-verdianos, mas sim na diáspora cabo-verdiana. Por isso pretende-se com essa dissertação procurar fazer um estudo, para saber qual a importância da Diáspora na política externa de Cabo Verde.

Assesing the political viability of labour market reform: The case of employment protection

We analyze the political support for employment protection legislation.Unlike my previous work on the same topic, this paper pays a lot ofattention to the role of obsolescence in the growth process.In voting in favour of employment protection, incumbent employeestrade off lower living standards (because employment protectionmaintains workers in less productive activities) against longer jobduration. The support for employment protection will then depend onthe value of the latter relative to the cost of the former. Wehighlight two key deeterminants of this trade-off: first, the workers'bargaining power, second, the economy's growth rate-more preciselyits rate of creative destruction.

Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling.

We previously reported that interleukin-1beta (IL-1beta) alone does not cause apoptosis of beta-cells, whereas when combined with gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), it exerts a distinct apoptotic effect. Studies in beta-cell lines indicated that IL-1beta reduced expression of islet brain (IB)-1/JNK interacting protein (JIP)-1, a JNK scaffold protein with antiapoptotic action. We examined whether variations in IB1/JIP-1 expression in purified primary beta-cells affect their susceptibility to cytokine-induced apoptosis. Exposure to IL-1beta for 24 h decreased cellular IB1/JIP-1 content by 66 +/- 17%; this IL-1beta effect was maintained in the presence of TNF-alpha + IFN-gamma, which did not influence IB1/JIP-1 levels by themselves. Addition of IL-1beta to TNF-alpha + IFN-gamma increased apoptosis from 20 +/- 2% to 59 +/- 5%. A similar increase in TNF-alpha + IFN-gamma-induced apoptosis was produced by adenoviral expression of antisense IB1/JIP-1 and was not further enhanced by addition of IL-1beta, indicating that IL-1beta-mediated suppression of IB1/JIP-1 in beta-cells increases their susceptibility to cytokine-induced apoptosis. However, adenovirally mediated overexpression of IB1/JIP-1 also potentiated TNF-alpha + IFN-gamma-induced apoptosis, suggesting that the antiapoptotic effect of IB1/JIP-1 depends on well-defined cellular levels. We conclude that the IB1/JIP-1 level in beta-cells can control their susceptibility to apoptosis independent of JNK signaling.

[Phot. du pont Valentré à Cahors par Eugène Chéron, en 1884, don J. Jackson en 1888]

Donateur : Jackson, James (1843-1895)

Le Bassin de Ribeira Seca de Santiago, Cap Vert - une gestion basée sur l´approche GIRE The Reservoir of Ribiera Seca de Santiago, Cape Vert - Management Exploitation GIRE

Dans cet article, l´auteur caractérise l´eau et l´agriculture des îles du Cap Vert et analyse les défis de l´eau après la construction du barrage de Poilao dans la Vallée de Ribeira Seca, sur l´île de Santiago, en se servant de l´approche GIRE (Gestion Intégrée des Ressources en Eau). Au niveau de la législation, il s´avère nécessaire de proposer de nouvelles lois, décrets et règlements qui soient en accord avec notre réalité, en opposition à un important lot d´instruments juridiques inapplicables, obsolètes et de compréhension difficile. La construction du barrage de Poilão a produit des impacts environnementaux, socio-économiques et sur l´irrigation. Il s´agit de trouver un modèle de gestion qui s´adapte à la réalité du Cap Vert et de l´île de Santiago, regroupant tous les partenaires pour une gestion durable de la vallée de Ribeira Seca et qui puisse servir d´exemple aux futurs barrages à construire.

Resistance to reform: Reconsidering the role of individual-specific uncertainty

Individual-specific uncertainty may increase the chances of reform beingenacted and sustained. Reform may be more likely to be enacted because amajority of agents might end up losing little from reform and a minoritygaining a lot. Under certainty, reform would therefore be rejected, butit may be enacted with uncertainty because those who end up losing believethat they might be among the winners. Reform may be more likely to besustained because, in a realistic setting, reform will increase theincentives of agents to move into those economic activities that benefit.Agents who respond to these incentives will vote to sustain reform infuture elections, even if they would have rejected reform under certainty.These points are made using the trade-model of Fernandez and Rodrik (AER,1991).

Translation to success of surgical innovation.

Contemporary thoracic and cardiovascular surgery uses extensive equipment and devices to enable its performance. As the specialties develop and new frontiers are crossed, the technology needs to advance in a parallel fashion. Strokes of genius or problem-solving brain-storming may generate great ideas, but the metamorphosis of an idea into a physical functioning tool requires a lot more than just a thinking process. A modern surgical device is the end-point of a sophisticated, complicated and potentially treacherous route, which incorporates new skills and knowledge acquisition. Processes including technology transfer, commercialisation, corporate and product development, intellectual property and regulatory routes all play pivotal roles in this voyage. Many good ideas may fall by the wayside for a multitude of reasons as they may not be marketable or may be badly marketed. In this article, we attempt to illuminate the components required in the process of surgical innovation, which we believe must remain in the remit of the modern-day thoracic and cardiovascular surgeon.