Deneysel Diyabet Modelinde Hipergliseminin Alzheimer Hastalığı ile İlişkili Proteinler Üzerine Etkisi

Abstract

Diabetes mellitus (DM) which is one of the foremost health problems enhances the risk of Alzheimer’s disease (AD) although the molecular mechanisms behind this association remain unclear. In the present study, selective Alzheimer’s disease indicator-1 (seladin-1) and insulin degrading enzyme (IDE) expressions were investigated in rat primary cultured neurons under diabetic conditions and in the brains of streptozotocine (STZ)-induced diabetic rats. We found that lack of insulin rather than high glucose levels decreased seladin-1 and IDE protein and mRNA levels in cultured rat primary neurons after 5 days incubation. If the diabetic conditions were intermittent, neuronal seladin-1 levels were unaffected whereas IDE levels were reduced. Increased BACE1 levels accompanied to decreased seladin-1 levels after 5 days of insulin deprivation. Metformin incubation in the presence of insulin increased seladin-1 protein and mRNA levels. Metformin and estradiol incubation with intermittent glucose treatment caused IDE to remain at control levels. STZ-induced diabetes reduced seladin-1 and IDE but did not change BACE1 levels in the brains of rats. Seladin-1 and IDE levels which were unchanged in the brains of ovariectomized rats decreased in STZ-induced diabetic and ovariectomized rats. Taken together we suggest that seladin-1 and IDE may represent new treatment targets for DM patients to prevent AD onset.