Sacubitril/valsartan treatment has differential effects in modulating diabetic kidney disease in db/db mice and KKAy mice compared with valsartan treatment

Author:

Myakala Komuraiah1,Jones Bryce A.2ORCID,Wang Xiaoxin X.1ORCID,Levi Moshe1ORCID

Affiliation:

1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, District of Columbia

2. Department of Pharmacology and Physiology, Georgetown University, Washington, District of Columbia

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.

Funder

American Heart Association

HHS | NIH | National Center for Advancing Translational Sciences

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Novartis

Publisher

American Physiological Society

Subject

Physiology

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