Combination of Exercise Training and Diet Restriction Normalizes Limited Exercise Capacity and Impaired Skeletal Muscle Function in Diet-Induced Diabetic Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 68-80 ◽  
Author(s):  
Tadashi Suga ◽  
Shintaro Kinugawa ◽  
Shingo Takada ◽  
Tomoyasu Kadoguchi ◽  
Arata Fukushima ◽  
...  

Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

2007 ◽  
Vol 39 (Supplement) ◽  
pp. S360
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Syoji Matsushima ◽  
Naoki Inoue ◽  
Yukihiro Ohta ◽  
...  

2018 ◽  
Vol 315 (3) ◽  
pp. R461-R468 ◽  
Author(s):  
Adam R. Konopka ◽  
Christopher A. Wolff ◽  
Miranda K. Suer ◽  
Matthew P. Harber

Intermuscular adipose tissue (IMAT) is associated with impaired skeletal muscle contractile and metabolic function. Myostatin and downstream signaling proteins such as cyclin-dependent kinase 2 (CDK2) contribute to the regulation of adipose and skeletal muscle mass in cell culture and animals models, but this relationship remains incompletely understood in humans. The purpose of this study was to determine if the infiltration of IMAT was associated with skeletal muscle myostatin and downstream proteins before and after 12 wk of aerobic exercise training (AET) in healthy older women (OW; 69 ± 2 yr), older men (OM; 74 ± 3 yr), and young men (YM; 20 ± 1 yr). We found that the infiltration of IMAT was correlated with myostatin and phosphorylated CDK2 at tyrosine 15 [P-CDK2(Tyr15)]. IMAT infiltration was greater in the older subjects and was associated with lower skeletal muscle function and exercise capacity. After 12 wk of AET, there was no change in body weight. Myostatin and P-CDK2(Tyr15) were both decreased after AET, and the reduction in myostatin was associated with decreased IMAT infiltration. The decrease in myostatin and IMAT occurred concomitantly with increased exercise capacity, skeletal muscle size, and function after AET. These findings demonstrate that the reduction in IMAT infiltration after AET in weight stable individuals was accompanied by improvements in skeletal muscle function and exercise capacity. Moreover, the association between myostatin and IMAT was present in the untrained state and in response to exercise training, strengthening the potential regulatory role of myostatin on IMAT.


2002 ◽  
Vol 92 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Espen E. Spangenburg ◽  
Simon J. Lees ◽  
Jeff S. Otis ◽  
Timothy I. Musch ◽  
Robert J. Talmadge ◽  
...  

It is thought that changes in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca2+ uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca2+ uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca2+ uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca2+handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.


2010 ◽  
Vol 109 (3) ◽  
pp. 702-709 ◽  
Author(s):  
C. R. Bueno ◽  
J. C. B. Ferreira ◽  
M. G. Pereira ◽  
A. V. N. Bacurau ◽  
P. C. Brum

The cellular mechanisms of positive effects associated with aerobic exercise training on overall intrinsic skeletal muscle changes in heart failure (HF) remain unclear. We investigated potential Ca2+ abnormalities in skeletal muscles comprising different fiber compositions and investigated whether aerobic exercise training would improve muscle function in a genetic model of sympathetic hyperactivity-induced HF. A cohort of male 5-mo-old wild-type (WT) and congenic α2A/α2C adrenoceptor knockout (ARKO) mice in a C57BL/6J genetic background were randomly assigned into untrained and trained groups. Exercise training consisted of a 8-wk running session of 60 min, 5 days/wk (from 5 to 7 mo of age). After completion of the exercise training protocol, exercise tolerance was determined by graded treadmill exercise test, muscle function test by Rotarod, ambulation and resistance to inclination tests, cardiac function by echocardiography, and Ca2+ handling-related protein expression by Western blot. α2A/α2CARKO mice displayed decreased ventricular function, exercise intolerance, and muscle weakness paralleled by decreased expression of sarcoplasmic Ca2+ release-related proteins [α1-, α2-, and β1-subunits of dihydropyridine receptor (DHPR) and ryanodine receptor (RyR)] and Ca2+ reuptake-related proteins [sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)1/2 and Na+/Ca2+ exchanger (NCX)] in soleus and plantaris. Aerobic exercise training significantly improved exercise tolerance and muscle function and reestablished the expression of proteins involved in sarcoplasmic Ca2+ handling toward WT levels. We provide evidence that Ca2+ handling-related protein expression is decreased in this HF model and that exercise training improves skeletal muscle function associated with changes in the net balance of skeletal muscle Ca2+ handling proteins.


2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Kechun Tang ◽  
George Murano ◽  
Peter D. Wagner ◽  
Ellen C. Breen

Sign in / Sign up

Export Citation Format

Share Document