Diabetes Mellitus’un Alzheimer İle Olası İlişkisi
Diabetes Mellitus, pankreasın insülin salgısının tam ya da kısmi yetersizliği ya da insülin etkisininyetersizliği ile oluşan, kendini hiperglisemi ile belli eden, karbonhidrat, lipid ve protein metabolizmabozukluğu ile de karakterize bir endokrin ve metabolizma hastalığıdır. Beyinde insülin reseptörlerininkeşfi ile insülinin beyin fizyolojisinde önemli bir rol oynadığı, serebral insülin sinyalinde ve glukozhomeostazında meydana gelen bozuklukların beyin patolojisine katkıda bulunduğu belirtilmektedir.İnsülin, reseptörü aracılığıyla kan-beyin bariyerini aşarak santral sinir sistemine girmekte, beyinglukoz metabolizmasında regülatör etkisine ek olarak, nöromodülatör ve nöroendokrin bir molekülgibi davranmakta, nöronal gelişim ve sağkalımda önemli bir rol almaktadır. İnsülin periferde olduğugibi, beyinde de etkilerini, reseptörü aracılığıyla, insülin reseptör substrat/fosfotidilinozitol 3-kinaz(IRS/PI3K) ve mitojen aktive protein kinaz (MAPK) sinyal yolu aracılığıyla göstermektedir. PI3Ksinyal yolağının aktivasyonu, protein kinaz B (Akt) aracılığı ile, Alzheimer’ın en belirgin ikipatolojik karakteristiği olan, tau hiperfosforilasyonu ile oluşan intraselüler nörofibriler yumaklar veβ-amiloid agregatlarının oluşturduğu ekstraselüler senil plakların metabolizmasının regülasyonundaetkili olmaktadır. Son yıllarda yapılan çalışmalarla, Alzheimer, Merkezi Sinir Sisteminde insülinreseptör duyarlılığının ve sinyal iletiminin bozulmasından kaynaklanan insülin rezistansınıngelişimine bağlı olarak meydana gelen tau ve Aβ metabolizmasındaki değişiklikleri içerdiğinden,Diabetes Mellitus’un beyin spesifik formu (Tip 3 DM) olarak tanımlanmaktadır.
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