Studies of SNAP-25 in regulated membrane fusion : metabolic consequences and tuning of intracellular Ca(2+) dynamics in beta cells

Increased release of insulin is usually regarded as a symptom of metabolic syndrome, contributing to insulin resistance in peripheral organs thus affecting glucose and insulin homeostasis. The existing animal models to address the metabolic syndrome are currently not optimal. In neuronal, neuroendocrine and endocrine cells, stimulus-dependent membrane fusion occurs via the SNARE complex, formed by the membrane-associated proteins SNAP-25 and syntaxin and the vesicle-associated protein VAMP-2, and requires intracellular Ca2+ elevations. The SNAP-25 protein exists as two splicing variants, SNAP-25a and SNAP-25b, differing in only 9 out of 206 amino acids. Both isoforms can mediate membrane fusion but their specific functions still remain unknown. In this thesis, we have investigated if an apparently small modification in the exocytotic machinery could act as triggering factor for development of metabolic syndrome. We used a genetically modified mouse expressing normal levels of SNAP-25, but with only the SNAP-25a isoform available. In Paper I, by monitoring a number of metabolic parameters during 7 weeks on control or Western (high fat/high sucrose) diet, we found that SNAP-25b-deficiency leads to metabolic syndrome, characterised by hyperinsulinemia, obesity, hyperglycaemia, liver steatosis and adipocyte hypertrophy. These conditions were even more pronounced when the mutation was combined with Western diet. The metabolic phenotype caused by SNAP-25b-deficiency was accompanied by increased insulin secretion from the islets of Langerhans partially involving beta cell hyperplasia in a sex dependent manner. In Paper II we addressed these issues closer and focused on islet physiology by monitoring intracellular Ca2+ dynamics in beta cells upon glucose stimulation. SNAP-25b-deficiency impaired the collective control of Ca2+ oscillations in beta cells with early initiation and delayed termination of activity as well as decreased synchronicity. Derangements of intracellular Ca2+ oscillatory patterns can be related to the increased insulin secretion found in SNAP-25b-deficient mice. In Paper III we observed that the SNAP-25 isoforms mediate different interactions with proteins important for the strict control of exocytosis both in neurons and beta cells, such as Munc18-1 and the Gβγ subunits of the heterotrimeric G proteins. In summary, we have shown that even a small modification in the machinery regulating membrane fusion, such as replacing SNAP-25b with SNAP-25a, acts as a triggering factor for the development of metabolic syndrome in mice. This condition was associated with loss of preciseness of Ca2+ oscillations in beta cells and increased insulin secretion. Thus, we propose the SNAP-25b-deficient mouse as a new model of metabolic syndrome and prediabetes

Historical and Cultural Perespectives on Slovenian Migrations

Znanstvena monografija odraža pestrost teoretičnih in metodoloških pristopov kot časovno in prostorsko širino obravnav. Avtorji obravnavajo odnos države in cerkve do izseljenstva (M. Drnovšek) slovensko izseljevanje intelektualcev v slovanski svet kot atipični pojav (I. Gantar Godina), emigrantsko literaturo in njeno mesto v slovenskem slovstvu in odnos domovine do nje (J. Žitnik), likovno umetnost kot vir za raziskovanje migracijske izkušnje z vidika ohranjanja in spreminjanja identitete (K. Toplak), žensko izseljevanje in njihove vloge pri ohranjanju etnične identitete v priseljenskem okolju (M. Milharčič Hladnik), vprašanja multikulturalizma v evropskih migracijskih procesih in hkrati kot element razpoznavnosti in identifikacijske drugačnosti v odnosih do priseljenske skupnosti (M. Lukšič Hacin)

Three social science disciplines in Central and Eastern Europe: handbook on economics, political science and sociology (1989-2001)

Content: Ulrike Becker, Max Kaase, Gabor Klaniczay, and Vera Sparschuh: Social Sciences in Central and Eastern Europe on the Verge of EU Enlargement (7-10); Andrei Plesu: Financing Difference. Fostering the Social Sciences in the Field of Tension Between Homogenization and Differentiation (12-16); Elemer Henkiss: Brilliant Ideas or Brilliant Errors? (17-24); Janos Matyas Kovacs: Business as (Un)usual (26-33); Mitko Dimitrov: Bulgaria (34-49); Frantisek Turnovec: Czech Republic (50-64); Tiia Püss: Estonia (65-82); Laszlo Csaba: Hungary (83-101); Raita Karnite: Latvia (102-120); Linas Cekanavicius: Lithuania (121-134); Tadeusz Kowalik: Poland (135-151); Paul Dragos Aligica: Romania (152-167); Julius Horvath: Slovakia (168-186); Joze Mencinger: Slovenia (187-194); Hans-Jürgen Wagener: Demand and Supply of Economic Knowledge in Transition Countries (195-203); Hans-Dieter Klingemann: Political Science in Central and Eastern Europe: National Development and International Integration (206-212); Georgi Karasimeonov: Bulgaria (213-225); Jan Holzer and Pavel Pseja: Czech Republic (226-245); Raivo Vetik: Estonia (246-257); Mate Szabo: Hungary (258-274); Andris Runcis: Latvia (275-285); Algis Krupavicius: Lithuania (286-305); Stanislaw Gebethner and Radoslaw Markowski: Poland (306-321); Daniel Barbu: Romania (322-342); Darina Malova and Silvia Mihalikova: Slovakia (343-357); Danica Fink-Hafner: Slovenia (358-374); Pal Tamas: Followers or Activists? Social Scientists in the Reality Shows of Transformation (376-385); Nikolai Genov: Bulgaria (386-404); Michal Illner: Czech Republic (405-424); Mikk Titma: Estonia (425-436); Denes Nemedi and Peter Robert: Hungary (437-451); Aivars Tabuns: Latvia (452-466); Anele Vosyliute: Lithuania (467-483); Janusz Mucha and Pawel Zalecki: Poland (484-501); Maria Larionescu: Romania (502-517); Zuzana Kusa, Bohumil Buzik, Ludovit Turcan and Robert Klobucky: Slovakia (518-535); Frane Adam and Matej Makarovic: Slovenia (536-547); Piotr Sztompka: The Condition of Sociology in East-Central Europe (548-556); Mihaly Sarkany: Cultural and Social Anthropology in Central and Eastern Europe (558-566); Thomas Kucera and Olga Kucerova: Population science in Central and Eastern Europe: Implications for Research and Practice (567-577); Marie-Claude Maurel: Central European Geography and the Post-Socialist Transformation. A Western Point of View (578-587); Grazyna Skapska: Law and Society in a Natural Laboratory: the Case of Poland in the Broader Context of East-Central Europe (588-603)