Insulin-independent glycogen supercompensation in isolated mouse skeletal muscle: role of phosphorylase inactivation

Sandström, Marie; Abbate, F.; Andersson, Daniel; Zhang, Shi‐Jin; Westerblad, Håkan; Katz, Abram

doi:10.1007/s00424-004-1280-7

Cited by 15 publications

(25 citation statements)

References 30 publications

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“…The low temperature was used to enhance viability of the muscle. We have shown previously that muscle viability is well maintained under such conditions, as judged by the ability to generate tetanic force (29). Furthermore, the extracellular space in muscles incubated for 19.5 h was virtually identical to those incubated for only 2 h (all muscles had values of 0.2-0.3 ml/g wet wt; BOH did not affect extracellular space under any condition studied).…”

Section: Materials and Animals 2-deoxymentioning

confidence: 70%

β-Hydroxybutyrate inhibits insulin-mediated glucose transport in mouse oxidative muscle

Yamada

Zhang

Westerblad

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Blood ketone body levels increase during starvation and untreated diabetes. Here we tested the hypothesis that ketone bodies directly inhibit insulin action in skeletal muscle. We investigated the effect of D,L-␤-hydroxybutyrate (BOH; the major ketone body in vivo) on insulin-mediated glucose uptake (2-deoxyglucose) in isolated mouse soleus (oxidative) and extensor digitorum longus (EDL; glycolytic) muscle. BOH inhibited insulin-mediated glucose uptake in soleus (but not in EDL) muscle in a time-and concentration-dependent manner. Following 19.5 h of exposure to 5 mM BOH, insulin-mediated (20 mU/ml) glucose uptake was inhibited by ϳ90% (substantial inhibition was also observed in 3-O-methylglucose transport). The inhibitory effect of BOH was reproduced with D-but not L-BOH. BOH did not significantly affect hypoxia-or AICAR-mediated (activates AMPdependent protein kinase) glucose uptake. The BOH effect did not require the presence/utilization of glucose since it was also seen when glucose in the medium was substituted with pyruvate. To determine whether the BOH effect was mediated by oxidative stress, an exogenous antioxidant (1 mM tempol) was used; however, tempol did not reverse the BOH effect on insulin action. BOH did not alter the levels of total tissue GLUT4 protein or insulin-mediated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 but blocked insulin-mediated phosphorylation of protein kinase B by ϳ50%. These data demonstrate that BOH inhibits insulin-mediated glucose transport in oxidative muscle by inhibiting insulin signaling. Thus ketone bodies may be potent diabetogenic agents in vivo. ketone bodies; soleus; extensor digitorum longus; glucose transporter 4

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Section: Materials and Animals 2-deoxymentioning

confidence: 70%

β-Hydroxybutyrate inhibits insulin-mediated glucose transport in mouse oxidative muscle

Yamada

Zhang

Westerblad

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Thereafter, they were stimulated to perform repeated tetanic contractions at 70 Hz (tetanic duration 100 ms, 2 trains/s) for 10 min and frozen in liquid N 2 within 10 s after termination of the last contraction. The stimulation protocol resulted in a marked loss of force (see RESULTS) but no irreversible damage as judged by a robust force recovery (28). Nonstimulated muscles from the contralateral leg served as controls and were incubated for 40 min in the same buffer at the same temperature.…”

Section: Experimental Designmentioning

confidence: 99%

Activation of aconitase in mouse fast-twitch skeletal muscle during contraction-mediated oxidative stress

Zhang¹,

Sandström²,

Lanner³

et al. 2007

American Journal of Physiology-Cell Physiology

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Aconitase is a mitochondrial enzyme that converts citrate to isocitrate in the tricarboxylic acid cycle and is inactivated by reactive oxygen species (ROS). We investigated the effect of exercise/contraction, which is associated with elevated ROS production, on aconitase activity in skeletal muscle. Humans cycled at 75% of maximal workload, followed by six 60-s bouts at 125% of maximum workload. Biopsies were taken from the thigh muscle at rest and after the submaximal and supramaximal workloads. Isolated mouse extensor digitorum longus (EDL; fast twitch) and soleus (slow twitch) muscles were stimulated to perform repeated contractions for 10 min. Muscles were analyzed for enzyme activities and glutathione status. Exercise did not affect aconitase activity in human muscle despite increased oxidative stress, as judged by elevated levels of oxidized glutathione. Similarly, repeated contractions did not alter aconitase activity in soleus muscle. In contrast, repeated contractions significantly increased aconitase activity in EDL muscle by approximately 50%, despite increased ROS production. This increase was not associated with a change in the amount of immunoreactive aconitase (Western blot) but was markedly inhibited by cyclosporin A, an inhibitor of the protein phosphatase calcineurin. Immunoprecipitation experiments demonstrated that aconitase was phosphorylated on serine residues. Aconitase in cell-free extracts was inactivated by the addition of the ROS hydrogen peroxide. In conclusion, the results suggest that aconitase activity can be regulated by at least two mechanisms: oxidation/reduction and phosphorylation/dephosphorylation. During contraction, a ROS-mediated inactivation of aconitase can be overcome, possibly by dephosphorylation of the enzyme. The dual-control system may be important in maintaining aerobic ATP production during muscle contraction.

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“…It has been shown [11] that a high carbohydrate diet following glycogen-depleting exercise leads to supercompensation of muscle glycogen stores, which remain stable above basal levels for up to several days. Supercompensation can be achieved in other situations such as refeeding after starvation [12], chronic low-frequency stimulation [13], or in cultured muscle cells subjected to hypoxia [14]. Despite significant efforts to study this phenomenon, its mechanisms are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Hexokinase 2, Glycogen Synthase and Phosphorylase Play a Key Role in Muscle Glycogen Supercompensation

et al. 2012

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BackgroundGlycogen-depleting exercise can lead to supercompensation of muscle glycogen stores, but the biochemical mechanisms of this phenomenon are still not completely understood.MethodsUsing chronic low-frequency stimulation (CLFS) as an exercise model, the tibialis anterior muscle of rabbits was stimulated for either 1 or 24 hours, inducing a reduction in glycogen of 90% and 50% respectively. Glycogen recovery was subsequently monitored during 24 hours of rest.ResultsIn muscles stimulated for 1 hour, glycogen recovered basal levels during the rest period. However, in those stimulated for 24 hours, glycogen was supercompensated and its levels remained 50% higher than basal levels after 6 hours of rest, although the newly synthesized glycogen had fewer branches. This increase in glycogen correlated with an increase in hexokinase-2 expression and activity, a reduction in the glycogen phosphorylase activity ratio and an increase in the glycogen synthase activity ratio, due to dephosphorylation of site 3a, even in the presence of elevated glycogen stores. During supercompensation there was also an increase in 5′-AMP-activated protein kinase phosphorylation, correlating with a stable reduction in ATP and total purine nucleotide levels.ConclusionsGlycogen supercompensation requires a coordinated chain of events at two levels in the context of decreased cell energy balance: First, an increase in the glucose phosphorylation capacity of the muscle and secondly, control of the enzymes directly involved in the synthesis and degradation of the glycogen molecule. However, supercompensated glycogen has fewer branches.

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Insulin-independent glycogen supercompensation in isolated mouse skeletal muscle: role of phosphorylase inactivation

Cited by 15 publications

References 30 publications

β-Hydroxybutyrate inhibits insulin-mediated glucose transport in mouse oxidative muscle

β-Hydroxybutyrate inhibits insulin-mediated glucose transport in mouse oxidative muscle

Activation of aconitase in mouse fast-twitch skeletal muscle during contraction-mediated oxidative stress

Hexokinase 2, Glycogen Synthase and Phosphorylase Play a Key Role in Muscle Glycogen Supercompensation

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