Endotelin-1’in diyabet patojenezindeki rolü

Diyabet (diabetes mellitus) yalnızca endokrin sistem hastalığı olmayıp, mikrovasküler ve makrovasküler komplikasyonlara neden olabilen bir damar hastalığıdır. Endotelyal işlevde bozukluk, endotel kaynaklı vazokonstriktör ve vazodilatör maddeler arasındaki dengenin bozulması sonucu gelişmekte, bu nedenle diyabet hastalarında görülen mikrovasküler ve makrovasküler komplikasyonların patojenezinde yer almakta veya bu komplikasyonların ilerlemesine neden olmaktadır. Bu komplikasyonlar “diyabetik vaskülopati” olarak adlandırılmaktadır. Endotelin-1 (ET-1) güçlü vazokonstriktör bir otakoit olmasının yanı sıra, proenflamatuvar, proliferatif ve profibrotik özellikleriyle diyabetik vaskülopatiye neden olabilmektedir. Diyabetik vaskülopatinin gelişimini engellemek için kullanılan terapötik hedefler endotel ve damar düz kas hücrelerindeki mekanizmalara yöneliktir. Diyabetik vaskülopati tedavisinde ET-1 reseptör antagonistlerinin kullanılabileceğine ilişkin deneysel ve klinik çalışmaların sonuçları umut vermektedir. Bu derlemede, diyabet patojenezinde ve insülin direncinin gelişmesinde ET-1’in rolüne değinilerek, özellikle diyabetik komplikasyonların önlenmesinde ET-1 reseptör antagonistlerinin olası terapötik yararı üzerinde durulmuştur.

Anahtar Kelimeler:

Endotelin-1, diabetes mellitus, oksidatif stres, insülin direnci, enflamasyon

The role of endothelin-1 in the pathogenesis of diabetes

Diabetes mellitus is not only an endocrine system disease, it is also a vascular disease which has microvascular and macrovascular complications. Endothelial dysfunction occurs due to an imbalance between endothelium-derived dilator and constrictor factors which has a role in the pathogenesis or progression of diabetes microvascular and macrovascular complications. These complications are named as “diabetic vasculopathy”. Endothelin-1 (ET-1) is a potent vasoconstrictor autacoid and also has proinflammatory, profibrotic, and proliferative properties which may contribute to diabetic vasculopathy. Endothelial and vascular smooth muscle cell mechanism are intended for therapeutic targets of diabetic vasculopathy. Clinical trials and experimental studies with ET-1 antagonists give a hope for diabetic vasculopaty treatments. This review focuses on the role of ET-1 in the pathogenesis of diabetes and insulin resistance and discusses the potential therapeutic benefit of targeting ET-1 receptor antagonists particularly in the prevention of diabetic complications.

Keywords:

Endothelin-1, diabetes mellitus, oxidative stress, insulin resistance, inflammation,

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