The therapeutic potential of IGF-I in skeletal muscle repair

Abstract

Skeletal muscle loss due to aging, motor neuron degeneration, cancer, heart failure and ischemia is a serious condition for which currently there is no effective treatment. Insulin-like growth factor 1 (IGF-I) plays an important role in muscle maintenance and repair. Preclinical studies have shown that IGF-I is involved in increasing muscle mass and strength, reducing degeneration, inhibiting the prolonged and excessive inflammatory process due to toxin injury and increasing the proliferation potential of satellite cells. However, clinical trials have not been successful due to ineffective delivery method. Choosing the appropriate isoforms or peptides and developing targeted delivery techniques can resolve this issue. Here we discuss the latest development in the field with special emphasis on novel therapeutic approaches.

TNF alpha inhibits myogenic differentiation of C2C12 cells through NF-κB activation and impairment of IGF-1 signaling pathway

“…Transgenic mice overexpressing IGF-1 specifically in the skeletal muscle promote muscle regeneration by reducing the expression of inflammatory cytokines such as TNF-a and IL-1b [34]. Furthermore, muscle specific expression of IGF-1 protect muscles from angiotensin II and denervation induced muscle atrophy through activation of Akt/mTOR pathway [16,35,36]. In the present study, we provided direct evidence that IGF-1 has the ability to prevent TNF-a induced inhibition of differentiation.…”

NRIP is a novel Z-disc protein to activate calmodulin signaling for skeletal muscle contraction and regeneration

“…Moreover, CaN transgenic mice display strong regeneration of skeletal muscle fibers after injury (Demonbreun et al, 2010;Stupka et al, 2006). In addition, the CaMK pathway can be activated by treatment with insulin-like growth factor 1 (IGF1), which has been well documented to activate satellite cells and to induce terminal myogenic differentiation (Lu et al, 2000;Song et al, 2013). Thus, NRIP promotes muscle regeneration through the CaN and CaMKII signaling pathways.…”

Skeletal muscle and pediatric bone development

“…Circulatory IGF-I concentrations mirror hepatic origins and both the muscle and bone secrete IGF-I, which acts in an autocrine and/or paracrine manner [51][52][53]. Breen et al [10] demonstrated prospectively a strong influence of IGF-I on adolescent bone mass accrual, such that the boys and girls in the 90th percentile of circulating IGF-I concentrations exhibited the greatest gains in bone mineral content (BMC) at various habitually loaded and unloaded skeletal regions.…”