A persistent increase in insulin-stimulated glucose uptake by both fast-twitch and slow-twitch skeletal muscles after a single exercise session by old rats

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

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Electrolytes in slow and fast muscle fibers of humans at rest and with dynamic exercise

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.245.1.r25 ◽

1983 ◽

Vol 245 (1) ◽

pp. R25-R31 ◽

Cited By ~ 17

Author(s):

G. Sjogaard

Keyword(s):

Skeletal Muscles ◽

Vastus Lateralis ◽

Fiber Types ◽

Triceps Brachii ◽

Sodium Potassium ◽

Mean Values ◽

Fiber Composition ◽

Slow Twitch ◽

Fast Twitch ◽

Muscle Fiber Membrane

Sodium, potassium, and magnesium were analyzed in human slow-twitch (ST) and fast-twitch (FT) skeletal muscles. In contrast to other species, no relation was found between fiber composition and electrolyte distribution. In soleus (S), vastus lateralis (VL), and triceps brachii (TB) the overall mean values for 6 men and 6 women were 44 mmol K/100 g dry wt and 11 mmol Na/100 g dry wt; the intracellular concentrations were 161 mmol K/l and 26 mmol Na/l with no differences between the muscles. Analysis of fragments of single ST and FT fibers from each of the muscles also showed no difference between the fiber types in Na and K content. Small differences were seen between the muscles with regard to Mg, but these were not related to fiber composition compared with other species. During exercise to exhaustion (3 bouts of bicycling for 3 min at 325-395 W, 6 men) the extracellular electrolyte concentrations for Na, K, and Mg increased from 134 to 140, 4.5 to 5.8, and 0.75 to 0.87 mmol/l, respectively (P less than 0.05). In VL Na content increased from 9.8 to 16.5 mmol/100 g dry wt, while intracellular [Na] remained constant. In contrast, intracellular [K] decreased from 161 to 141 mmol/l (P less than 0.05). No such changes occurred in TB. In concert with other studies the present changes in electrolytes in the working muscles indicate that muscle fatigue may be related to changes at the muscle fiber membrane.

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Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice

BMC Genomics ◽

10.1186/s12864-020-07225-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Pabodha Hettige ◽

Uzma Tahir ◽

Kiisa C. Nishikawa ◽

Matthew J. Gage

Keyword(s):

Skeletal Muscles ◽

Striated Muscle ◽

Fiber Type ◽

Expression Patterns ◽

Fiber Types ◽

Muscle Adaptation ◽

Myosin Heavy Chain Isoform ◽

Genes Encoding ◽

Slow Twitch ◽

Fast Twitch

Abstract Background Individual skeletal muscles have evolved to perform specific tasks based on their molecular composition. In general, muscle fibers are characterized as either fast-twitch or slow-twitch based on their myosin heavy chain isoform profiles. This approach made sense in the early days of muscle studies when SDS-PAGE was the primary tool for mapping fiber type. However, Next Generation Sequencing tools permit analysis of the entire muscle transcriptome in a single sample, which allows for more precise characterization of differences among fiber types, including distinguishing between different isoforms of specific proteins. We demonstrate the power of this approach by comparing the differential gene expression patterns of extensor digitorum longus (EDL), psoas, and soleus from mice using high throughput RNA sequencing. Results EDL and psoas are typically classified as fast-twitch muscles based on their myosin expression pattern, while soleus is considered a slow-twitch muscle. The majority of the transcriptomic variability aligns with the fast-twitch and slow-twitch characterization. However, psoas and EDL exhibit unique expression patterns associated with the genes coding for extracellular matrix, myofibril, transcription, translation, striated muscle adaptation, mitochondrion distribution, and metabolism. Furthermore, significant expression differences between psoas and EDL were observed in genes coding for myosin light chain, troponin, tropomyosin isoforms, and several genes encoding the constituents of the Z-disk. Conclusions The observations highlight the intricate molecular nature of skeletal muscles and demonstrate the importance of utilizing transcriptomic information as a tool for skeletal muscle characterization.

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Glucose uptake and metabolic stress in rat muscles stimulated electrically with different protocols

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.3.1237 ◽

2001 ◽

Vol 91 (3) ◽

pp. 1237-1244 ◽

Cited By ~ 33

Author(s):

Rune Aslesen ◽

Ellen M. L. Engebretsen ◽

Jesper Franch ◽

Jørgen Jensen

Keyword(s):

Glucose Uptake ◽

Wistar Rats ◽

Metabolic Stress ◽

Reduction In Force ◽

Tracer Amount ◽

Slow Twitch ◽

Fast Twitch ◽

The Relationship ◽

Glycogen Breakdown

In the present study, the relationship between the pattern of electrical stimulation and glucose uptake was investigated in slow-twitch muscles (soleus) and fast-twitch muscles (epitrochlearis) from Wistar rats. Muscles were stimulated electrically for 30 min in vitro with either single pulses (frequencies varied between 0.8 and 15 Hz) or with 200-ms trains (0.1–2 Hz). Glucose uptake (measured with tracer amount of 2-[3H]deoxyglucose) increased with increasing number of impulses whether delivered as single pulses or as short trains. The highest glucose uptake achieved with short tetanic contractions was similar in soleus and epitrochlearis (10.9 ± 0.7 and 12.0 ± 0.8 mmol · kg dry wt−1 · 30 min−1, respectively). Single pulses, on the other hand, increased contraction-stimulated glucose uptake less in soleus than in epitrochlearis (7.5 ± 1.1 and 11.7 ± 0.5 mmol · kg dry wt−1 · 30 min−1, respectively; P < 0.02). Glucose uptake correlated with glycogen breakdown in soleus ( r = 0.84, P < 0.0001) and (epitrochlearis: r = 0.91, P < 0.0001). Contraction-stimulated glucose uptake also correlated with breakdown of ATP and PCr and with reduction in force. Our data suggest that metabolic stress mediates contraction-stimulated glucose uptake.

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Pretranslational regulation of myoglobin gene expression

AJP Cell Physiology ◽

10.1152/ajpcell.1987.252.4.c450 ◽

1987 ◽

Vol 252 (4) ◽

pp. C450-C453 ◽

Cited By ~ 35

Author(s):

L. E. Underwood ◽

R. S. Williams

Keyword(s):

Gene Expression ◽

Tibialis Anterior ◽

Skeletal Muscles ◽

Blot Hybridization ◽

Oxidative Capacity ◽

Striated Muscles ◽

Mrna Content ◽

Slow Twitch ◽

Rna Probe ◽

Fast Twitch

We have used blot hybridization techniques and a specific anti-sense RNA probe to determine whether variation in myoglobin gene expression among mammalian striated muscles is attributable to pretranslational regulatory events. We observed that myoglobin mRNA was expressed to approximately 10- and 5-fold greater levels, respectively, in cardiac and soleus (slow-twitch, oxidative, skeletal) muscles of adult rabbits than in tibialis anterior (fast-twitch, glycolytic, skeletal) muscles. Furthermore, when oxidative capacity of tibialis anterior muscles was increased by 21 days of indirect electrical stimulation, a model of exercise conditioning, myoglobin mRNA content increased approximately 15-fold. We conclude that pretranslational mechanisms are important in regulation of myoglobin gene expression in mammalian muscles.

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Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle glucose uptake

Journal of Applied Physiology ◽

10.1152/japplphysiol.01009.2001 ◽

2002 ◽

Vol 92 (3) ◽

pp. 1285-1292 ◽

Cited By ~ 26

Author(s):

Desmond G. Hunt ◽

Zhenping Ding ◽

John L. Ivy

Keyword(s):

Glucose Uptake ◽

Kinase Activity ◽

Pi3 Kinase ◽

Intracellular Concentration ◽

Insulin Receptor Substrate ◽

Phosphatidylinositol 3 Kinase ◽

Rat Skeletal Muscle ◽

Slow Twitch ◽

Chronic Clenbuterol ◽

Fast Twitch

In the present study, we investigated the effects of chronic clenbuterol treatment on insulin-stimulated glucose uptake in the presence of epinephrine in isolated rat skeletal muscle. Insulin (50 μU/ml) increased glucose uptake in both fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles. In the presence of 24 nM epinephrine, insulin-stimulated glucose uptake was completely suppressed. This suppression of glucose uptake by epinephrine was accompanied by an increase in the intracellular concentration of glucose 6-phosphate and a decrease in insulin-receptor substrate-1-associated phosphatidylinositol 3-kinase (IRS-1/PI3-kinase) activity. Clenbuterol treatment had no direct effect on insulin-stimulated glucose uptake. However, after clenbuterol treatment, epinephrine was ineffective in attenuating insulin-stimulated muscle glucose uptake. This ineffectiveness of epinephrine to suppress insulin-stimulated glucose uptake occurred in conjunction with its inability to increase the intracellular concentration of glucose 6-phosphate and attenuate IRS-1/PI3-kinase activity. Results of this study indicate that the effectiveness of epinephrine to inhibit insulin-stimulated glucose uptake is severely diminished in muscle from rats pretreated with clenbuterol.

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Influence of Temperature on the Isometric Myograms of Cross Innervated Mammalian Fast Twitch and Slow Twitch Skeletal Muscles

Nature ◽

10.1038/218877a0 ◽

1968 ◽

Vol 218 (5144) ◽

pp. 877-878 ◽

Cited By ~ 11

Author(s):

A. J. BULLER ◽

K. W. RANATUNGA ◽

JANET SMITH

Keyword(s):

Skeletal Muscles ◽

Influence Of Temperature ◽

Influence Of Temperature On ◽

Slow Twitch ◽

Fast Twitch

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Prior treatment with the AMPK activator AICAR induces subsequently enhanced glucose uptake in isolated skeletal muscles from 24-month-old rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0858 ◽

2018 ◽

Vol 43 (8) ◽

pp. 795-805 ◽

Cited By ~ 6

Author(s):

Kentaro Oki ◽

Edward B. Arias ◽

Makoto Kanzaki ◽

Gregory D. Cartee

Keyword(s):

Glucose Uptake ◽

Skeletal Muscles ◽

Glucose Transporter ◽

Ex Vivo ◽

Prior Treatment ◽

Male Rats ◽

Protein Abundance ◽

Transporter Protein ◽

Old Rats ◽

Exercise Induced

5′ AMP-activated protein kinase (AMPK) activation may be part of the exercise-induced process that enhances insulin sensitivity. Independent of exercise, acute prior treatment of skeletal muscles isolated from young rats with a pharmacological AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), causes subsequently improved insulin-stimulated glucose uptake (GU). However, efficacy of a single prior AICAR exposure on insulin-stimulated GU in muscles from old animals has not been studied. The purpose of this study was to determine whether brief, prior exposure to AICAR (3.5 h before GU assessment) leads to subsequently increased GU in insulin-stimulated skeletal muscles from old rats. Epitrochlearis muscles from 24-month-old male rats were isolated and initially incubated ±AICAR (60 min), followed by incubation without AICAR (3 h), then incubation ±insulin (50 min). Muscles were assessed for GU (via 3-O-methyl-[3H]-glucose accumulation) and site-specific phosphorylation of key proteins involved in enhanced GU, including AMPK, Akt, and Akt substrate of 160 kDa (AS160), via Western blotting. Prior ex vivo AICAR treatment resulted in greater GU by insulin-stimulated muscles from 24-month-old rats. Prior AICAR treatment also resulted in greater phosphorylation of AMPK (T172) and AS160 (S588, T642, and S704). Glucose transporter type 4 (GLUT4) protein abundance was unaffected by prior AICAR and/or insulin treatment. These findings demonstrate that skeletal muscles from older rats are susceptible to enhanced insulin-stimulated GU after brief activation of AMPK by prior AICAR. Consistent with earlier research using muscles from young rodents, increased phosphorylation of AS160 is implicated in this effect, which was not attributable to altered GLUT4 glucose transporter protein abundance.

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Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00659.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. E966-E978 ◽

Cited By ~ 41

Author(s):

Naveen Sharma ◽

Edward B. Arias ◽

Abhijit D. Bhat ◽

Donel A. Sequea ◽

Steve Ho ◽

...

Keyword(s):

Glucose Uptake ◽

Insulin Dose ◽

Heat Shock Protein 90 ◽

Regulatory Proteins ◽

Phosphatidylinositol 3 Kinase ◽

Akt Phosphorylation ◽

Pi3k Activity ◽

Phosphatase 2A ◽

Slow Twitch ◽

Fast Twitch

Calorie restriction [CR; ∼65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-mo-old male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[3H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr308and Ser473) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle- and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser588and Thr642) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows: 1) elevated Akt phosphorylation is fundamental, regardless of muscle or insulin dose; 2) altered Akt binding to regulatory proteins (HSP90 and unidentified Akt partners) is involved in the effects of CR on Akt phosphorylation; 3) Akt effects on GU depend on muscle- and insulin dose-specific elevation in phosphorylation of Akt substrates, including, but not limited to, AS160; and 4) greater IR phosphorylation and aPKC activity may contribute at higher insulin doses.

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