Defective insulin/IGF-I signaling and loss of myonuclei in skeletal muscle of patients with chronic kidney disease (CKD)

Studies in animals have shown that uremia interacts with IRS signaling, leading to defective AKT phosphorylation, and that this process may lead to caspase activation and accelerated proteolysis. In a previous study, we observed that apoptotic loss of myonuclei is enhanced in CKD-Stage 5 patients and that this finding couples with defective AKT phosphorylation, suggesting that altered insulin signalling is responsible for defective regeneration of muscle myofiber. In this study we evaluated the occurrence of cell loss by apoptosis, as well as of changes in myostatin gene expression and MAPK-related cellular signaling in muscle biopsies of patients with advanced CKD.