The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals.

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Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus) or glycolytic (EDL) muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK), Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK) and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1), mechano-growth factor (MGF) and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group.

No abstract