IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice

Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering From muscle wasting conditions, few studies have investi gated the functional properties of dystrophic skeletal muscle following [CF -I treatment. 129Pl ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer fr om a deficiency in the structural protein, laminin. and exhibit severe musc le wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I tre atment(similar to2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutane ously) would increase the mass and force producing capacity of skeletal mus cles from dystrophic mice. IGF-I treatment increased the mass of the extens or digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 2 9%. respectively, compared with untreated dystrophic mice administered sali ne-vehicle only). Absolute maximum force (P-o) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Spec ific P-o (sP(o)) was increased by 23% in the EDL muscles of treated compare d with untreated mice, but in the soleus muscle sP(o) uas unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decr eased the proportion of type I fibres in the EEL muscles of dystrophic mice . In the soleus muscles of dystrophic mice. IGF-I treatment increased the p roportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus mus cles of treated compared with untreated mice. We conclude that IGF-I treatm ent ameliorates muscle wasting and improves the functional properties of sk eletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the m uscular dystrophies. (C) 2001 Elsevier Science B.V. All rights reserved.