Sacubitril/valsartan treatment has differential effects in modulating diabetic kidney disease in <i>db/db</i> mice and KKAy mice compared with valsartan treatment
Komuraiah Myakala, Bryce A. Jones, Xiaoxin X. Wang, Moshe Levi
Abstract
The first-in-class drug sacubitril/valsartan, a combination of the angiotensin II receptor blocker valsartan and neprilysin inhibitor sacubitril, was tested for its effects in diabetic kidney disease using db/db mice and KKAy mice. We found that Sac/Val has sufficient therapeutical potential to counter the pathophysiological effects of diabetic kidney disease. We further revealed a new mechanism to cause inflammation, self-DNA-activated cGAS-STING signaling, which was activated in diabetic kidneys and prevented by sacubitril/valsartan or valsartan treatment.
Topics & Concepts
ValsartanSacubitrilMedicineInternal medicineEndocrinologyNeprilysinAngiotensin receptorDiabetes mellitusKidneyPharmacologySacubitril, ValsartanAngiotensin IIReceptorChemistryBlood pressureEnzymeBiochemistryinterferon and immune responsesCytokine Signaling Pathways and InteractionsRNA modifications and cancer