THE EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1 AND NERVE GROWTH FACTOR ON DENERVATED MUSCLE ATROPHY

Abstract

The effects of growth factors on denervated muscle atrophy in mouse gastrocnemius muscle were studied by morphometric, physiologic and histologic methods. Fifteen mice were randomized into three groups: intact, denervated-insulin-like growth factor-1-treated (D-IGF-1) and denervated-nerve growth factor-treated (D-NGF). In denervated animals, the left sides were used as a control by injecting balanced salt solution (HBSS), while the right sides were injected with growth factors. The mean wet weight and the mean wet weight/body weight were significantly higher in D-IGF-1 muscles compared to the D-NGF and D-HBSS muscles, but were not different from the muscle of intact controls. Physiologic testing showed that the mean maximal tetanic twitch strength and the mean maximal fast twitch strength were also significantly higher in the D-IGF-1 muscles than in the D-NGF and D-HBSS muscles. Mean time-to-peak was significantly only decreased in the D-NGF muscles. Histological studies found that the mean percentage of type 2 fiber was significantly higher in D-NGF muscles. The types I and II mean diameters in the D-IGF-1 muscles were larger than in the D-NGF and D-HBSS muscles, but all denervated muscles had higher interstitial fibrosis than the intact controls. In conclusion, we show that IGF-1 can effectively retard denervated muscle atrophy by increasing types I and II fibre muscle diameter. However, IGF-1 cannot prevent interstitial fibrosis in the denervated muscle.