The present study was undertaken to test the hypothesis that the direct action of IGF-I infusion would lead to an increase in muscle DNA as well as various measurements of muscle size. Either 0.9% saline or non-systemic doses of recombinant human IGF-I (rhIGF-1) were injected directly into an unloaded rat muscle, the tibialis anterior muscle (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. The infusion of physiological saline had no effect on the mass, protein or DNA content of the TA muscle. Local infusion of IGF-I had no effect on body weight or heart weight. The absolute weight of injected TA muscle was ~9% greater (P<0.05) than the weight of the contralateral TA muscle. IGF-I infusion resulted in a significant increase in total protein and DNA content in TA muscle (P<0.05). As a result of these concerted changes, the DNA to protein ratio of the hypertrophied TA muscle was the same as in the contralateral muscles. These results suggest that IGF-I may act to directly stimulate processes such as protein synthesis and satellite cell proliferation leading to skeletal muscle hypertrophy.

IGF-1 and skeletal muscle hypertrophy

The details of the mechanisms and pathways by which mechanical stress stimulates local hypertrophy of muscle fibres are still being elucidated. However, it is clear that growth hormone (GH), fibroblast growth factors (FGF) and insulin-like growth factors (IGF) play a central role in this process. Levels of insulin-like growth factor I (IGF-I) peptide have been shown to increase in overloaded skeletal muscle (GR Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In this study, an increase of IGF-1 was observed to measurably increase muscle protein and correlate with an increase in muscle DNA content. Several other studies have shown that muscle fibres undergoing hypertrophy due to mechanical stress express elevated levels of IGF-I before hypertrophy.

IGF-1 appears to be an important regulator of nuclear-cytoplasmic ratio. Studies have shown that the muscle will only undergo hypertrophy if the cell volume-to-nucleus ratio can be kept within a finite limit. In the above study, 0.9-1.9 µg/kg/day of rhIGF-1 was injected into a relatively “unstressed” muscle, the tibialis anterior muscle, which then simulated the effects of exercise on the muscle. There was an increase in protein content, cross-sectional area and DNA content. It is suggested that the increase in muscle DNA is a result of increased proliferation and differentiation of satellite cells, which give up their nuclei when they fuse with damaged or hypertrophic muscle cells. Note that the quantities of IGF-1 used in the injections were extremely low, much lower than in studies that have shown relatively poor results from systemic IGF-1 administration, which range from 1.0 to 6.9 milligrams/kg/day.

IGF-1 and skeletal muscle hypertrophy

All the attention and discussion about injecting fat into muscles to increase limb girth is just a symptom of the obsessive nature of bodybuilding. I might suggest that topical injections of small amounts (micrograms) of rhIGF-1 to increase individual muscle growth would be a much better alternative to fat injections, eciclene or even silicone implants. National or professional level bodybuilders with lagging calves would be wise to consider the results of this study if they come across a bottle of Genentech rhIGF-1!

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