Publikationsserver der Universitätsbibliothek Marburg
Titel:Einfluss von Glukose auf die HMGB-1-Regulation der ß-Inselzellen
Autor:Depboylu, Aysegül
Weitere Beteiligte: Schäfer, Helmut (Prof. Dr.)
Veröffentlicht:2014
URI:https://archiv.ub.uni-marburg.de/diss/z2014/0528
DOI: https://doi.org/10.17192/z2014.0528
URN: urn:nbn:de:hebis:04-z2014-05284
DDC:610 Medizin
Titel (trans.):Influence of glucose on the HMGB-1-regulation of pancreatic ß-cells
Publikationsdatum:2014-07-09
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Gastroenterology, Gastroenterologie

Zusammenfassung:
In der vorliegenden Arbeit wurde der Einfluss von Glukose auf die HMGB1-Regulation von Glukose der ß-Inselzellen untersucht. INS-1 Zellen, die mit 10 und 30 mM Glukose behan-delt wurden, wurden mittels 2 D-Gelelektrophorese aufgetrennt. Wir untersuchten die Pro-teine HMGB1 und Caspase 3, die anschließend mit Hilfe von Westernblot verifiziert wur-den. Unter der Hyperglykämie zeigte sich eine Herunterregulation von HMGB1 sowie eine Aktivierung von Caspase 3. Ferner wurde mit Hilfe von MTT-Assays unter hypergly-kämischen Bedingungen eine signifikante Abnahme der Zellproliferation nachgewiesen. Bei der Zellfraktionierung konnte unter erhöhter Glukosebelastung eine Reduktion von HMGB1 sowohl im Zellkern als auch im Zytosol dargestellt werden. Eine zusätzliche Be-handlung mit Pioglitazon konnte interessanterweise eine Herabregulation von HMGB1 verhindern. Die mit 10 mM Glukose und Pioglitazon behandelten INS-Zellen zeigten eine deutliche Unterexpression bzw. eine starke Beeinträchtigung der Zellproliferation. In Anbe-tracht dessen entfaltet Pioglitazon seine protektive Wirkung unter erhöhten Glukose-bedingungen. Bei den Diabetikern wurden vor und nach der Pioglitazonbehandlung er-niedrigte HMGB1-Spiegel nachgewiesen. Eine Erhöhung der HMGB1-Spiegel konnte un-ter Einfluss von Pioglitazon nicht erzielt werden. In der Zusammenschau der Befunde ist anzunehmen, dass Pioglitazon seine protektive Wirkung erst im fortgeschrittenen Stadium des Diabetes Mellitus entfaltet. Desweiteren entfaltet Pioglitazon seine protektive Wirkung auf die Karzinomzellen, so dass ein Harn-blasenkarzinom oder Kolonkarzinom verursacht wird. In Anbetracht dessen wurden Glitazone 2011 vom Markt genommen. Pioglitazon soll aber ggf. bei MS wirksam sein. Um mögliche antiapoptotische Funktionen von HMGB1 zu untersuchen, wurde mittels RT-PCR eine Klonierung, dann eine stabile Transfektion durchgeführt. In den durchgeführten Westernblots zeigte sich eine leichtgradige HMGB1-Überexpression. Wir gingen von einer leichten Überexpression aus, da sich die stabil transfizierten INS-1 Zellen im Vergleich zu den normalen INS-1 Zellen anders verhielten. Unter erhöhten Glukosekonzrentrationen stellte sich keine Herunterregulation der HMGB1-Bande dar und die Zellproliferation der INS-1 Klone war deutlich gebessert. Eine Caspase 3-Spaltung konnte unter erhöhten Glukosebedingungen nicht nachgewiesen werden, somit verhindert eine HMGB1-Überexpression die Aktivierung von Caspase 3.

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