Projekti

Project title: Tight junction signalling in the adaptation of the insulin-producing beta cells

Project number: 127935

Funding Instrument: International Co-operation: SCOPES (Scientific Co-operation with Eastern Europe)

Project Duration: 1.11.2009 - 31.10.2012

Amount Granted: CHF 135.000,00


Principal Applicant

Professeur Paolo Meda
Dépt. Physiologie Cellulaire et Métabolisme
Faculté de Médecine
Université de Genève
Centre Médical Universitaire
Rue Michel-Servet 1
CH-1211 Genève 4


Co-applicant(s)

Professor Zakira Mornjakovic
Institute of Histology
School of Medicine
University of Sarajevo
Cekalusa, 90
BA-71000 Sarajevo
Fax: +387 33 20 36 69
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Assistant Professor Almira Hadzovic-Dzuvo
Department of Physiology
School of Medicine
University of Sarajevo
Cekalusa 90
BA-71000 Sarajevo
Phone: +38 761143154
Fax: +38 73 3651014
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Research Institutions

1. Dépt. Physiologie Cellulaire et Métabolisme
Faculté de Médecine
Université de Genève

2. Centre Médical Universitaire
Rue Michel-Servet 1
CH-1211 Genève 4
University of Geneva

3.Institute of Histology
School of Medicine
University of Sarajevo
Cekalusa, 90
BA-71000 Sarajevo

4. Department of Physiology
School of Medicine
Cekalusa 90
University of Sarajevo

 

Main objectives of the project

The beta cells of pancreatic islets, which produce insulin and are central to the development of diabetes, are linked by tight junctions. These membrane regions seal the intercellular spaces, separate the apical from the baso-lateral cell membrane and provide channels for ion transport. The composition of these membrane domains and their physiological function are still unknown in beta cells. Based on preliminary observations, we hypothesize that tight junction proteins play a central role in controlling the adaptation of beta cells to increasing metabolic demand (during pregnancy) and control their resistance to an immunologic attack (at the onset of diabetes). This project will test these possibilities by combining the expertise of the Sarajevo and Geneva partners. Specifically, we plan to 1) characterize the normal pattern of tight junction proteins in the beta cells of control rodent and human beta cells, 2) evaluate the changes of these proteins during rodent pregnancy and 3) as a function of diabetes development in the NOD mouse model, 4) study how the changes in tight junction proteins may affect the permeability barrier and the flux of intercellular signals within pancreatic islets and 5) investigate whether tight junctions are altered by in beta cell cultures exposed to hormones and cytokines prevailing in the islet environment during pregnancy and the onset of diabetes, respectively. The project will provide information on a native component of the beta cell membrane, which is deemed important for the proper function of the insulin-producing cells.

Keywords: tight junctions, intercellular junctions, claudins, ZO, NOD, occludin, pregnancy, JAM, diabetes