High protein ingestion does not affect whole-body insulin sensitivity

Diet is critical in type 2 diabetes management, with high-protein diets (HPD), rich in branched-chain amino acids (BCAAs), proposed to enhance glycemic control, but overactivation of S6K1-related signaling pathway may contribute to IR pathogenesis by impairing insulin-stimulated glucose uptake in skeletal muscle. The study objective was to investigate the impact of varying dietary protein interventions on insulin sensitivity (IS) and molecular signaling in skeletal muscle in overweight or obese individuals, both acutely and over an up to 18-weeks period. The analysis performed in the 18-week data set used a subset of data with available adipose tissue biopsies randomised, controlled, isoenergetic dietary intervention, focusing on the here relevant HPD and control diets. IS was assessed using labelled intravenous glucose tolerance tests (IVGTT) in the acute study, while the euglycemic-hyperinsulinemic clamp (EHC) was used in the 18-week intervention. Key protein implicated in insulin signalling, such as IP6K1 and total AMPK protein content significantly decreased following the HP meal, alongside an increased p-AktThr ³⁰⁸ /Akt2 activity while S6K1 mRNA was lower after 6 weeks of HPD, compared to the control diet group, but not at 18 weeks. However, these differences at the molecular level did not translate into significant changes in whole-body IS.