**Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy**

#### **Tadashi Yoshida 1,2,\* and Patrice Delafontaine 1,2,\***


Received: 1 July 2020; Accepted: 19 August 2020; Published: 26 August 2020

**Abstract:** Insulin-like growth factor-1 (IGF-1) is a key growth factor that regulates both anabolic and catabolic pathways in skeletal muscle. IGF-1 increases skeletal muscle protein synthesis via PI3K/Akt/mTOR and PI3K/Akt/GSK3β pathways. PI3K/Akt can also inhibit FoxOs and suppress transcription of E3 ubiquitin ligases that regulate ubiquitin proteasome system (UPS)-mediated protein degradation. Autophagy is likely inhibited by IGF-1 via mTOR and FoxO signaling, although the contribution of autophagy regulation in IGF-1-mediated inhibition of skeletal muscle atrophy remains to be determined. Evidence has suggested that IGF-1/Akt can inhibit muscle atrophy-inducing cytokine and myostatin signaling via inhibition of the NF-κB and Smad pathways, respectively. Several miRNAs have been found to regulate IGF-1 signaling in skeletal muscle, and these miRs are likely regulated in di fferent pathological conditions and contribute to the development of muscle atrophy. IGF-1 also potentiates skeletal muscle regeneration via activation of skeletal muscle stem (satellite) cells, which may contribute to muscle hypertrophy and/or inhibit atrophy. Importantly, IGF-1 levels and IGF-1R downstream signaling are suppressed in many chronic disease conditions and likely result in muscle atrophy via the combined e ffects of altered protein synthesis, UPS activity, autophagy, and muscle regeneration.

**Keywords:** insulin-like growth factor-1; skeletal muscle; hypertrophy; atrophy; cachexia; muscle regeneration; autophagy
