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Publication
Role of phosphoinositide 3-OH kinase p110ß in skeletal myogenesis.
Authors Matheny RW, Riddle-Kottke MA, Leandry LA, Lynch CM, Abdalla MN, Geddis AV, Piper
DR, Zhao JJ
Submitted By Submitted Externally on 5/18/2015
Status Published
Journal Molecular and cellular biology
Year 2015
Date Published
Volume : Pages 35 : 1182 - 1196
PubMed Reference 25605332
Abstract 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 ß (p110ß) in myogenesis and metabolism. In C2C12 cells, pharmacological
inhibition of p110ß delayed differentiation. We next generated mice with
conditional deletion of p110ß in skeletal muscle (p110ß muscle knockout
[p110ß-mKO] mice). While young p110ß-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
p110ß-mKO mice were less glucose tolerant than old control mice. Overexpression
of p110ß accelerated differentiation in C2C12 cells and primary human myoblasts
through an Akt-dependent mechanism, while expression of kinase-inactive p110ß
had the opposite effect. p110ß overexpression was unable to promote myoblast
differentiation under conditions of p110a inhibition, but expression of p110a
was able to promote differentiation under conditions of p110ß inhibition. These
findings reveal a role for p110ß during myogenesis and demonstrate that
long-term reduction of skeletal muscle p110ß impairs whole-body glucose
tolerance without affecting skeletal muscle size or strength in old mice.




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