Effect of work-induced hypertrophy on muscle glucose metabolism in lean and obese mice

Abstract

Summary. The effect of work-induced hypertrophy (without any concomitant change in circulating parameters) on skeletal muscle metabolism was studied in lean mice and in goldthioglucose obese-mice. Soleus muscle was functionally overloaded in one leg by tenotomy of gastrocnemius muscle 4 days before muscle isolation, muscle in the other leg being used as control. Basal deoxyglucose uptake and glycolysis were markedly increased in overloaded muscles compared with control muscles, together with a ten-fold increase in fructose 2-6 bisphosphate content. In the presence of maximally effective insulin concentrations, deoxyglucose uptake and glycolysis were identical in overloaded and control muscles of lean mice, while the effects of overload and insulin were partly additive in muscles of goldthioglucose-obese mice. The sensitivity to insulin and insulin binding to muscles were not modified in overloaded muscles. Insulin-stimulated glycogenogenesis was decreased by about 50% probably due to a lower amount of glycogen synthase in overloaded than in control muscles. Thus, in muscles of goldthioglucose-obese mice work-induced hypertrophy increased the response to maximal insulin concentrations without modifying the altered insulin sensitivity and decreased insulin binding. Key words:Insulin, insulin resistance, obesity, exercise, glucose metabolism, glycogen synthase, fructose 2-6 bisphosphate, skeletal muscle, goldthioglucose obese mice, hypertrophy.Muscle tissue from obese hyperinsulinaemic animals displays a number of abnormalities including a defect in glucose transport and utilization, an altered aminoacid transport and a decrease in insulin binding [1][2][3][4][5]. This results in decreased insulin sensitivity and responsiveness of this tissue, which largely contribute to the marked insulin resistance observed in genetically-or experimentally-induced obese syndromes. In normal man and animals it has been demonstrated repeatedly that physical training is associated with an increase in overall insulin sensitivity in vivo [6][7][8][9][10][11]; skeletal muscle seems to contribute essentially to this increased insulin sensitivity [9][10][11]. In obese animals, although physical training by treadmill running or by swimming improves tolerance, insulin resistance in muscle is either unchanged [7,8] or partly reversed [7].In the present study, we used the following approach. By cutting the connection of the gastrocnemius muscle to the ankle of one single leg, an important work load is applied to the soleus muscle which undergoes rapid compensatory hypertrophy [12]. Taking advantage of this experimental technique, we compared a hypertrophied, overloaded muscle in one leg with a control muscle in the other within the same animal, and we studied the effect of this form of exercise on glucose uptake and metabolism in lean and goldthioglucose-obese mice. Materials and methods AnimalsMale Swiss albino mice (age 7-8 weeks) were fed ad libitum with laboratory chow (Usine d'Alimentation Rationnelle, Villemoisson, Epinay/Orge, France)...

GLUT4 Is Not Necessary for Overload-Induced Glucose Uptake or Hypertrophic Growth in Mouse Skeletal Muscle

“…2 A ). These findings are in contrast with previous work in mouse soleus in which a 30-min preincubation with phloridzin (5 mmol/L) impaired basal and overload-induced glucose uptake 70–75% (6). Since the current study allowed a longer time (60 min) for phloridzin diffusion to the innermost muscle fibers, the discrepancy between these findings is most likely due to inhibitor dose.…”

“…4). These findings, along with previous work that showed that 4 days of overload increased soleus muscle glucose uptake ∼80% in male mice that were 25–30 weeks old (6), demonstrate that overload can stimulate muscle glucose uptake irrespective of fiber type, sex, or age.…”

“…In rodents, chronic muscle loading (overload) can be achieved via surgical ablation of synergist muscles or tendons (6–9), and studies have shown that it rapidly and consistently induces adaptations in skeletal muscle similar to resistance training, such as muscle hypertrophy (6–9). In both insulin-sensitive and insulin-resistant mouse muscle, 3–4 days of overload is sufficient to increase muscle mass (30–40%) (6–8) and glucose uptake (∼80%) (6), suggesting that resistance training and overload may use the same cellular mechanisms to regulate muscle metabolism. Unfortunately, these mechanisms are not well understood.…”

Effect of exercise on protein turnover in muscles of lean and obese mice

“…Muscles of the unoperated contralateral legs were used as controls, since there was no difference between muscles from sham-operated or from non-operated legs [12, data not shown]. Four days after the operation (when the hypertrophy reached a plateau [13]), mice were killed by cervical dislocation and soleus muscles were isolated and incubated as previously described [11] in I ml Krebs-Ringer bicarbonate buffer (pH 7.3) containing pyruvate (2 retool/l). The additions were specified in each experiment.…”

“…Mice injected with goldthioglucose were obese, slightly hyperglycaemic and markedly hyperinsulinaemic, and thus were insulin-resistant. Four days after tenotomizing the gastrocnemius muscle, work-induced hypertrophy of the soleus muscle was [13]. Since oedema occurs in hypertrophied muscles [13,22], muscle growth was measured as the accumulation of protein rather than as changes in muscle wet weight.…”