Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models

TLDR

The IGF1‑Akt/PKB signaling cascade is a highly conserved pathway that regulates skeletal muscle growth by controlling protein synthesis through mTOR and GSK3β and protein degradation via FoxO, and while essential during development and regeneration, its role in adult muscle response to mechanical load remains unclear. This review aims to elucidate the composition and function of the IGF1‑Akt/PKB pathway in skeletal muscle fibers by synthesizing evidence from transgenic and knockout mouse models and muscle transient transfection experiments. The authors analyze pathway components and their interactions using in vivo genetic models and transient transfection studies to map the signaling network governing muscle growth.

Abstract

A highly conserved signaling pathway involving insulin-like growth factor 1 (IGF1), and a cascade of intracellular components that mediate its effects, plays a major role in the regulation of skeletal muscle growth. A central component in this cascade is the kinase Akt, also called protein kinase B (PKB), which controls both protein synthesis, via the kinases mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3β (GSK3β), and protein degradation, via the transcription factors of the FoxO family. In this paper, we review the composition and function of this pathway in skeletal muscle fibers, focusing on evidence obtained in vivo by transgenic and knockout models and by muscle transient transfection experiments. Although this pathway is essential for muscle growth during development and regeneration, its role in adult muscle response to mechanical load is less clear. A full understanding of the operation of this pathway could help to design molecularly targeted therapeutics aimed at preventing muscle wasting, which occurs in a variety of pathologic contexts and in the course of aging.