Glucagon-Like Peptide-1 Protects Human Islets against Cytokine-Mediated β-Cell Dysfunction and Death: A Proteomic Study of the Pathways Involved

Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic β-cells against cytokine-induced dysfunction and destruction. The mechanisms through which GLP-1 exerts its effects are complex and still poorly understood. The aim of this study was to analyze the protein expression profiles of human islets of Langerhans treated with cytokines (IL-1β and IFN-γ) in the presence or absence of GLP-1 by 2D difference gel electrophoresis and subsequent protein interaction network analysis to understand the molecular pathways involved in GLP-1-mediated β-cell protection. Co-incubation of cytokine-treated human islets with GLP-1 resulted in a marked protection of β-cells against cytokine-induced apoptosis and significantly attenuated cytokine-mediated inhibition of glucose-stimulated insulin secretion. The cytoprotective effects of GLP-1 coincided with substantial alterations in the protein expression profile of cytokine-treated human islets, illustrating a counteracting effect on proteins from different functional classes such as actin cytoskeleton, chaperones, metabolic proteins, and islet regenerating proteins. In summary, GLP-1 alters in an integrated manner protein networks in cytokine-exposed human islets while protecting them against cytokine-mediated cell death and dysfunction. These data illustrate the beneficial effects of GLP-1 on human islets under immune attack, leading to a better understanding of the underlying mechanisms involved, a prerequisite for improving therapies for diabetic patients.status: publishe

The Czech and Irish Protocols to the Lisbon Treaty: negotiation and argumentation of small states

This bachelor thesis focuses on negotiation strategies used by "small states" that are defined in the theoretical part of the thesis. In the form of a case study, the thesis analyses Irish and Czech approach to negotiations on the exemptions from the Treaty of Lisbon, that were put forward by political representation of both countries. The so- called small states use, due to their limited economic and personal resources, specifically aimed activities in order to gain favorable negotiating positions within the European Union. Both Ireland and Czech Republic are, according to the typology used, classified as "small states". During the ratification process of the Treaty of Lisbon, the European Union encountered obstacles caused by the result of the first Irish referendum and by the stance of Czech President Václav Klaus, regarding the completion of the ratification process. These obstacles led to the formulation of specific demands that were presented to the European Union. This thesis examines the strategies that were used in this stage of the ratification process to achieve legal guarantees for Ireland and Czech Republic. These strategies are analyses using official documents and public statements of national and European political elites. In its conclusive part the thesis states the applied..