Energetic driving forces are maintained in resting rat skeletal muscle after dietary creatine supplementation

2001 ◽  
Vol 90 (1) ◽  
pp. 62-66 ◽  
Author(s):  
J. McMillen ◽  
C. M. Donovan ◽  
J. I. Messer ◽  
W. T. Willis

The total creatine (TCr) pool of skeletal muscle is composed of creatine (Cr) and phosphocreatine (PCr). In resting skeletal muscle, the ratio of PCr to TCr (PCr/TCr; PCr energy charge) is ∼0.6–0.8, depending on the fiber type. PCr/TCr is linked to the cellular free energy of ATP hydrolysis by the Cr kinase equilibrium. Dietary Cr supplementation increases TCr in skeletal muscle. However, many previous studies have reported data indicating that PCr/TCr falls after supplementation, which would suggest that Cr supplementation alters the resting energetic state of myocytes. This study investigated the effect of Cr supplementation on the energy phosphates of resting skeletal muscle. Male rats were fed either rodent chow (control) or chow supplemented with 2% (wt/wt) Cr. After 2 wk on the diet, the gastrocnemius and soleus muscles were freeze clamped and removed from anesthetized animals. Cr supplementation increased TCr, PCr, and Cr levels in the gastrocnemius by 20, 22, and 17%, respectively ( P < 0.05). A numerical 6% higher mean soleus TCr in Cr-supplemented rats was not statistically significant. All other energy phosphate concentrations, free energy of ATP hydrolysis, and PCr/TCr were not different between the two groups in either muscle. We conclude that Cr supplementation simply increased TCr in fast-twitch rat skeletal muscle but did not otherwise alter resting cellular energetic state.

2007 ◽  
Vol 17 (6) ◽  
pp. 624-634 ◽  
Author(s):  
Jeffrey J. Brault ◽  
Theodore F. Towse ◽  
Jill M. Slade ◽  
Ronald A. Meyer

Short-term creatine supplementation is reported to result in a decreased ratio of phosphocreatine (PCr) to total creatine (TCr) in human skeletal muscle at rest. Assuming equilibrium of the creatine kinase reaction, this decrease in PCr:TCr implies increased cytoplasmic ADP and decreased Gibbs free energy of ATP hydrolysis in muscle, which seems contrary to the reported ergogenic benefits of creatine supplementation. This study measured changes in PCr and TCr in vastus lateralis muscle of adult men (N = 6, 21–35 y old) during and 1 day after 5 d of creatine monohydrate supplementation (0.43 g·kg body weight−1·d−1) using noninvasive 31P and 1H magnetic-resonance spectroscopy (MRS). Plasma and red-blood-cell creatine increased by 10-fold and 2-fold, respectively, by the third day of supplementation. MRS-measured skeletal muscle PCr and TCr increased linearly and in parallel throughout the 5 d, and there was no significant difference in the percentage increase in muscle PCr (11.7% ± 2.3% after 5 d) vs. TCr (14.9% ± 4.1%) at any time point. The results indicate that creatine supplementation does not alter the PCr:TCr ratio, and hence the cytoplasmic Gibbs free energy of ATP hydrolysis, in human skeletal muscle at rest.


2021 ◽  
Vol 22 (14) ◽  
pp. 7588
Author(s):  
Zoltan Gombos ◽  
Erika Koltai ◽  
Ferenc Torma ◽  
Peter Bakonyi ◽  
Attila Kolonics ◽  
...  

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.


1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.


2000 ◽  
Vol 278 (3) ◽  
pp. E398-E404 ◽  
Author(s):  
Bo Falck Hansen ◽  
Wim Derave ◽  
Pia Jensen ◽  
Erik A. Richter

We examined whether the protein level and/or activity of glycogenin, the protein core upon which glycogen is synthesized, is limiting for maximal attainable glycogen levels in rat skeletal muscle. Glycogenin activity was 27.5 ± 1.4, 34.7 ± 1.7, and 39.7 ± 1.3 mU/mg protein in white gastrocnemius, red gastrocnemius, and soleus muscles, respectively. A similar fiber type dependency of glycogenin protein levels was seen. Neither glycogenin protein level nor the activity of glycogenin correlated with previously determined maximal attainable glycogen levels, which were 69.3 ± 5.8, 137.4 ± 10.1, and 80.0 ± 5.4 μmol/g wet wt in white gastrocnemius, red gastrocnemius, and soleus muscles, respectively. In additional experiments, rats were exercise trained by swimming, which resulted in a significant increase in the maximal attainable glycogen levels in soleus muscles (∼25%). This increase in maximal glycogen levels was not accompanied by an increase in glycogenin protein level or activity. Furthermore, even in the presence of very high glycogen levels (∼170 μmol/g wet wt), ∼30% of the total glycogen pool continued to be present as unsaturated glycogen molecules (proglycogen). Therefore, it is concluded that glycogenin plays no limiting role for maximal attainable glycogen levels in rat skeletal muscle.


2019 ◽  
Vol 316 (5) ◽  
pp. E695-E706 ◽  
Author(s):  
Mark W. Pataky ◽  
Carmen S. Yu ◽  
Yilin Nie ◽  
Edward B. Arias ◽  
Manak Singh ◽  
...  

Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple fiber types, but exercise’s effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2 wk) and were either sedentary (SED) or exercised (2-h exercise). Other, low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately postexercise (IPEX) or 3 h postexercise (3hPEX). Epitrochlearis muscles from IPEX rats were incubated in 2-deoxy-[3H]glucose (2-[3H]DG) without insulin. Epitrochlearis muscles from 3hPEX rats were incubated with 2-[3H]DG ± 100 µU/ml insulin. After single fiber isolation, GU and fiber type were determined. Glycogen and lipid droplets (LDs) were assessed histochemically. GLUT4 abundance was determined by immunoblotting. In HFD-SED vs. LFD-SED rats, insulin-stimulated GU was decreased in type IIB, IIX, IIAX, and IIBX fibers. Insulin-independent GU IPEX was increased and glycogen content was decreased in all fiber types (types I, IIA, IIB, IIX, IIAX, and IIBX). Exercise by HFD-fed rats enhanced insulin-stimulated GU in all fiber types except type I. Single fiber analyses enabled discovery of striking fiber type-specific differences in HFD and exercise effects on insulin-stimulated GU. The fiber type-specific differences in insulin-stimulated GU postexercise in insulin-resistant muscle were not attributable to a lack of fiber recruitment, as indirectly evidenced by insulin-independent GU and glycogen IPEX, differences in multiple LD indexes, or altered GLUT4 abundance, implicating fiber type-selective differences in the cellular processes responsible for postexercise enhancement of insulin-mediated GLUT4 translocation.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Jaume Padilla ◽  
Nathan T Jenkins ◽  
Jeffrey S Martin ◽  
Jacqueline M Crissey ◽  
Shawn B Bender ◽  
...  

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