SRP407920 PRJNA901501 GSE217975 Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet ß cells in mice Type 2 Diabetes Mellitus (T2DM) is a severe disease that has reached epidemic proportions. In this study, treatment of T2DM mice with young, undamaged, and ultrapure recombinant mouse serum albumin (rMSA) increased their serum albumin levels, which resulted in a reversal of the disease including reduced fasting blood glucose levels, improved glucose tolerance, increased glucose-stimulated insulin secretion, and alleviated islet atrophy. At the cellular level, rMSA improved glucose uptake and glycolysis in hepatocytes. Mechanistically, rMSA reduced the binding between CAV1 and EGFR to increase EGFR activation leading to PI3K-AKT activation. Furthermore, rMSA extracellularly reduced the rate of fatty acid uptake by islet ß-cells, which relieved the accumulation of intracellular ceramide, endoplasmic reticulum stress, and apoptosis. This study provided the first clear demonstration that injections of young, undamaged, and ultrapure recombinant serum albumin can alleviate T2DM in mice. Overall design: A total of 6 liver samples from mice i.v. injected with isometric saline (n=3) or rMSA (n=3; 1.5g/kg b.w.) for 9 weeks were randomly selected to explore the chronic effects of rMSA on the hepatic gene expression profile. The AML12 hepatocytes were respectively treated with vehicle, insulin (10 nM), rMSA (600 µM), or insulin+rMSA for 24h and subjected to RNA-seq. GSE217975 pubmed 36747238