Losartan, an angiotensin II type 1 receptor blocker, protects human islets from glucotoxicity through the phospholipase C pathway. Anne-Marie Madec,*,1,2 ...
The FASEB Journal • Research Communication
Losartan, an angiotensin II type 1 receptor blocker, protects human islets from glucotoxicity through the phospholipase C pathway Anne-Marie Madec,*,1,2 Roméo Cassel,*,1 Séverine Dubois,* Sylvie Ducreux,† Guillaume Vial,* Marie-Agnès Chauvin,* Aurélia Mesnier,* Karim Chikh,* Domenico Bosco,‡ Jennifer Rieusset,* Fabien Van Coppenolle,† and Charles Thivolet*,§ *Institut National de la Santé et de la Recherche Médicale (INSERM) U1060/Université Lyon 1, Lyon-Sud Medicine Faculty, Oullins, France; †INSERM U1060/Université Lyon 1, Rockefeller Medicine Faculty, Lyon, France; ‡Cell Isolation and Transplantation Centre, Geneva University Hospital, Geneva, Switzerland; and §Department of Endocrinology and Diabetes, Hospices Civils de Lyon (HCL), Université Lyon 1, Lyon, France As shown in a large clinical prospective trial, inhibition of the renin-angiotensin system (RAS) can delay the onset of type 2 diabetes in high-risk individuals. We evaluated the beneficial effects of RAS inhibition on -cell function under glucotoxic conditions. Human islets from 13 donors were cultured in 5.5 mM (controls) or 16.7 mM glucose [high glucose (HG)] for 4 d with or without losartan (5 M), a selective AT1R blocker, and/or U73122 (2 M), a selective PLC inhibitor, during the last 2 d. HG induced RAS activation with overexpression of AT1R (P
