ADAM17 cleaves the insulin receptor ectodomain on endothelial cells and causes vascular insulin resistance
Thaysa Ghiarone, Jorge A. Castorena‐Gonzalez, Christopher Foote, Francisco I. Ramirez‐Perez, Larissa Ferreira‐Santos, Francisco J. Cabral-Amador, Roger de la Torre, Rama Ganga, Andrew A. Wheeler, Camila Manrique‐Acevedo, Jaume Padilla, Luis A. Martinez‐Lemus
Abstract
To our knowledge, this is the first study to investigate the involvement of ADAM17 in causing impaired insulin-induced vasodilation in T2D. We provide evidence that ADAM17 activity is increased in the vasculature of patients with T2D and support the notion that ADAM17-mediated shedding of endothelial IRα ectodomains is a novel mechanism causing vascular insulin resistance. Our results highlight that targeting ADAM17 activity may be a potential therapeutic strategy to correct vascular insulin resistance in T2D.