P-Rex1 limits glucose clearance and suppresses hepatocyte glucose uptake and mitochondrial metabolism independently of its Rac-GEF activity
Julia Y. Chu, Elpida Tsonou, Polly A. Machin, Kirsty MacLellan-Gibson, Anna G. Roberts, Stephen A. Chetwynd, Adam T. McCormack, John C. Stephens, Elisa Benetti, Gemma K. Kinsella, David Baker, David C. Hornigold, Heidi C. E. Welch
October, 2025Abstract
This paper shows that P-Rex1 limits glucose clearance and suppresses hepatocyte glucose uptake and mitochondrial metabolism through a catalysis-independent function, alongside its established Rac-GEF-dependent role in fasting glucose control and insulin sensitivity. It positions P-Rex1 as a regulator of liver glucose homeostasis through both catalytic and non-catalytic mechanisms.