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. 2017 Oct 26:8:830.
doi: 10.3389/fphys.2017.00830. eCollection 2017.

Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

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Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

Marco A S Fortes et al. Front Physiol. .

Abstract

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.

Keywords: electrostimulation; hyperglycemia; muscle mass regulation; muscle strength; protein synthesis; skeletal muscle.

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Figures

Figure 1
Figure 1
Body weight (A) and glycaemia (B) of control and diabetic rats during 4 weeks of the experiments. Results are expressed as mean ± SEM of 13 animals. ***p < 0.001, using repeated measures two-way ANOVA followed by Bonferroni post-test. CTRL, control group; DM, diabetic group.
Figure 2
Figure 2
Cross-sectional areas (CSA) of the EDL muscle fibers. (A) Representative histological hematoxylin and eosin staining images of EDL muscle CSA. Reference bar represents 50 μm. (B) Dispersion graph of EDL muscle fibers CSA. (C) Frequency distribution of the EDL muscle fibers according to CSA ranges: 0–5,500 μm2. The results were analyzed as previously described using the 95% confidence interval of the median. *Significant different considering the 95% confidence interval of the median. CTRL-CL, control group, contralateral muscle; CTRL-H, control group, hypertrophied muscle; DM-CL, diabetic group, contralateral muscle; DM-H, diabetic group, hypertrophied muscle.
Figure 3
Figure 3
Cross-sectional areas (CSA) of the soleus muscle fibers. (A) Representative histological hematoxylin and eosin staining images of the soleus muscle CSA. Reference bar represents 50 μm. (B) Dispersion graph of soleus muscle fibers CSA. (C) Frequency distribution of the soleus muscle fibers according to the CSA ranges: 0–7,000 μm2. The results were analyzed as previously described using the 95% confidence interval of the median. *Significant difference considering the 95% confidence interval of the median. CTRL-CL, control group, contralateral muscle; CTRL-H, control group, hypertrophied muscle; DM-CL, diabetic group, contralateral muscle; DM-H, diabetic group, hypertrophied muscle.
Figure 4
Figure 4
(A–D, F–I) Contents of signaling proteins associated with protein synthesis and degradation in the EDL muscle after 7 days of overload. Quantitative analysis of western blotting of total and phosphorylated Akt, rpS6, AMPK, MuRF-1 and atrogin-1 of the EDL muscle. Results are expressed as mean ± SEM of at least six animals. *p < 0.05, **p < 0.01, ***p < 0.001 using two-way ANOVA followed by Bonferroni post-test. In (E,J), *p < 0.05 CTRL-CL/DM-CL vs. CTRL-H/DM-H using two-way ANOVA only. CTRL, Control group; DM, Diabetic group; CL, Contralateral; H, Hypertrophy. Western blotting gels and ponceau staining are presented in Supplementary Material.
Figure 5
Figure 5
(A–D, F,H,J) Contents of signaling proteins associated with protein synthesis and degradation in the soleus muscle after 7 days of overload. Quantitative analysis of western blotting of total and phosphorylated Akt, rpS6, AMPK, MuRF-1 and atrogin-1 of the soleus muscle. Data are expressed as mean ± SEM of at least six animals. *p < 0.05, **p < 0.01, ***p < 0.001 using two-way ANOVA followed by Bonferroni post-test. In (E), #p < 0.05 for CTRL vs. DM and *p < 0.05 for CTRL-CL/DM-CL vs. CTRL-H/DM-H, in (G), *p < 0.05 for CTRL-CL/DM-CL vs. CTRL-H/DM-H, in (I), *p < 0.05 for CTRL-CL/DM-CL vs. CTRL-H/DM-H using two-way ANOVA only. Control group; DM, Diabetic group; CL, Contralateral muscle; H, Hypertrophied muscle. Western blotting gels and ponceau staining are presented in Supplementary Material.
Figure 6
Figure 6
(A,B,D, F–M) mRNA expression of several genes in the EDL muscle after 7 days of overload. Results are presented as mean ± SEM of at least six animals. Results were analyzed using two-way ANOVA followed by Bonferroni post-test. *p < 0.05, **p < 0.01. In (C), #p < 0.05 for CTRL-CL/DM-CL vs. CTRL-H/DM-H, in (E), #p < 0.05 for CTRL vs. DM using two-way ANOVA only. CL, Contralateral muscle; H, Hypertrophied muscle; DM, Diabetic group; CTRL, Control group.
Figure 7
Figure 7
(A–F, H–K, M) mRNA expression of several genes in the soleus muscle after 7 days of overload. Results are presented as mean ± SEM of at least nine animals. Data were analyzed using two-way ANOVA followed by Bonferroni post-test. *p < 0.05, **p < 0.01, ***p < 0.001. In (G), *p < 0.05 CTRL vs. DM and #p < 0.05 for CTRL-CL/DM-CL vs. CTRL-H/DM-H, in (L), #p < 0.05 for CTRL-CL/DM-CL vs. CTRL-H/DM-H using two-way ANOVA only. CL, Contralateral muscle; H, Hypertrophied muscle; DM, Diabetic group; CTRL, Control group.
Figure 8
Figure 8
Main signaling pathways involved in the hypertrophy of the soleus and EDL muscles. (A) Effect of the early diabetic condition upon mRNA content and (B) modulation of the main signaling pathways involved in the hypertrophy of the soleus and EDL muscles in control or diabetic animals and in both.

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References

    1. Andersen H., Gadeberg P. C., Brock B., Jakobsen J. (1997). Muscular atrophy in diabetic neuropathy: a stereological magnetic resonance imaging study. Diabetologia 40, 1062–1069. 10.1007/s001250050788 - DOI - PubMed
    1. Andersen H., Gjerstad M. D., Jakobsen J. (2004). Atrophy of foot muscles: a measure of diabetic neuropathy. Diabetes Care 27, 2382–2385. 10.2337/diacare.27.10.2382 - DOI - PubMed
    1. Andersen H., Poulsen P. L., Mogensen C. E., Jakobsen J. (1996). Isokinetic muscle strength in long-term IDDM patients in relation to diabetic complications. Diabetes 45, 440–445. 10.2337/diab.45.4.440 - DOI - PubMed
    1. Armstrong D. D., Esser K. A. (2005). Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Am. J. Physiol. Cell Physiol. 289, C853–C859. 10.1152/ajpcell.00093.2005 - DOI - PubMed
    1. Armstrong D. D., Wong V. L., Esser K. A. (2006). Expression of beta-catenin is necessary for physiological growth of adult skeletal muscle. Am. J. Physiol. Cell Physiol. 291, C185–C188. 10.1152/ajpcell.00644.2005 - DOI - PubMed

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