| First Author | Matheny RW Jr | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 7 | Pages | 1182-96 |
| PubMed ID | 25605332 | Mgi Jnum | J:224289 |
| Mgi Id | MGI:5661989 | Doi | 10.1128/MCB.00550-14 |
| Citation | Matheny RW Jr, et al. (2015) Role of phosphoinositide 3-OH kinase p110beta in skeletal myogenesis. Mol Cell Biol 35(7):1182-96 |
| abstractText | Phosphoinositide 3-OH kinase (PI3K) regulates a number of developmental and physiologic processes in skeletal muscle; however, the contributions of individual PI3K p110 catalytic subunits to these processes are not well-defined. To address this question, we investigated the role of the 110-kDa PI3K catalytic subunit beta (p110beta) in myogenesis and metabolism. In C2C12 cells, pharmacological inhibition of p110beta delayed differentiation. We next generated mice with conditional deletion of p110beta in skeletal muscle (p110beta muscle knockout [p110beta-mKO] mice). While young p110beta-mKO mice possessed a lower quadriceps mass and exhibited less strength than control littermates, no differences in muscle mass or strength were observed between genotypes in old mice. However, old p110beta-mKO mice were less glucose tolerant than old control mice. Overexpression of p110beta accelerated differentiation in C2C12 cells and primary human myoblasts through an Akt-dependent mechanism, while expression of kinase-inactive p110beta had the opposite effect. p110beta overexpression was unable to promote myoblast differentiation under conditions of p110alpha inhibition, but expression of p110alpha was able to promote differentiation under conditions of p110beta inhibition. These findings reveal a role for p110beta during myogenesis and demonstrate that long-term reduction of skeletal muscle p110beta impairs whole-body glucose tolerance without affecting skeletal muscle size or strength in old mice. |
