Pluto Bioinformatics

GSE124394: Role of p110a subunit of PI3-kinase in skeletal muscle mitochondria

Bulk RNA sequencing

Skeletal muscle insulin resistance, decreased phosphatidylinositol 3-kinase (PI3K) activation and altered mitochondrial function are hallmarks of type 2 diabetes. We created mice with a muscle-specific knockout of p110 or p110, the two major catalytic subunits of PI3K. We find that mice with muscle-specific knockout of p110, but not p110, display impaired muscle insulin signaling and reduced muscle size due to enhanced proteasomal and autophagic activity. Despite insulin resistance and muscle atrophy, M-p110KO mice show decreased serum myostatin, increased mitochondrial mass, increased mitochondrial fusion visualized by intravital microscopy, and increased PGC1 expression, especially PCG12 and PCG13. This leads to enhanced mitochondrial oxidative capacity, striking increases in muscle NADH content, and higher muscle free radical release measured in vivo using pMitoTimer reporter. Thus, p110 is the dominant catalytic isoform of PI3K in muscle in control of insulin sensitivity and muscle mass, and has a unique role in mitochondrial homeostasis in skeletal muscle. SOURCE: Hui Pan (Hui.Pan@joslin.harvard.edu) - Joslin Diabetes Center