Transgenic mice overexpressing GLUT-1 protein in muscle exhibit increased muscle glycogenesis after exercise

2000 ◽  
Vol 278 (4) ◽  
pp. E588-E592 ◽  
Author(s):  
Jian-Ming Ren ◽  
Nicole Barucci ◽  
Bess A. Marshall ◽  
Polly Hansen ◽  
Mike M. Mueckler ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Progressive Increase ◽  
Second Phase ◽  
Glycogen Accumulation ◽  
Glut 1 ◽  
Glycogen Concentration ◽  
High Level ◽  
Muscle Glycogen Concentration

The purpose of the present study was to determine the rates of muscle glycogenolysis and glycogenesis during and after exercise in GLUT-1 transgenic mice and their age-matched littermates. Male transgenic mice (TG) expressing a high level of human GLUT-1 and their nontransgenic (NT) littermates underwent 3 h of swimming. Glycogen concentration was determined in gastrocnemius and extensor digitorum longus (EDL) muscles before exercise and at 0, 5, and 24 h postexercise, during which food (chow) and 10% glucose solution (as drinking water) were provided. Exercise resulted in ∼90% reduction in muscle glycogen in both NT (from 11.2 ± 1.4 to 2.1 ± 1.3 μmol/g) and TG (from 99.3 ± 4.7 to 11.8 ± 4.3 μmol/g) in gastrocnemius muscle. During recovery from exercise, the glycogen concentration increased to 38.2 ± 7.3 (5 h postexercise) and 40.5 ± 2.8 μmol/g (24 h postexercise) in NT mice. In TG mice, however, the increase in muscle glycogen concentration during recovery was greater (to 57.5 ± 7.4 and 152.1 ± 15.7 μmol/g at 5 and 24 h postexercise, respectively). Similar results were obtained from EDL muscle. The rate of 2-deoxyglucose uptake measured in isolated EDL muscles was 7- to 10-fold higher in TG mice at rest and at 0 and 5 h postexercise. There was no difference in muscle glycogen synthase activation measured in gastrocnemius muscles between NT and TG mice immediately after exercise. These results demonstrate that the rate of muscle glycogen accumulation postexercise exhibits two phases in TG: 1) an early phase (0–5 h), with rapid glycogen accumulation similar to that of NT mice, and 2) a progressive increase in muscle glycogen concentration, which differs from that of NT mice, during the second phase (5–24 h). Our data suggest that the high level of steady-state muscle glycogen in TG mice is due to the increase in muscle glucose transport activity.

Effect of glycogen synthase overexpression on insulin-stimulated muscle glucose uptake and storage

2004 ◽  
Vol 286 (3) ◽  
pp. E363-E369 ◽  
Author(s):  
Donovan L. Fogt ◽  
Shujia Pan ◽  
Sukho Lee ◽  
Zhenping Ding ◽  
Angus Scrimgeour ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Transgenic Mice ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Wild Type ◽  
Effect Relationship ◽  
Glycogen Concentration ◽  
Cause And Effect ◽  
Muscle Glycogen Concentration

Insulin-stimulated muscle glucose uptake is inversely associated with the muscle glycogen concentration. To investigate whether this association is a cause and effect relationship, we compared insulin-stimulated muscle glucose uptake in noncontracted and postcontracted muscle of GSL3-transgenic and wild-type mice. GSL3-transgenic mice overexpress a constitutively active form of glycogen synthase, which results in an abundant storage of muscle glycogen. Muscle contraction was elicited by in situ electrical stimulation of the sciatic nerve. Right gastrocnemii from GSL3-transgenic and wild-type mice were subjected to 30 min of electrical stimulation followed by hindlimb perfusion of both hindlimbs. Thirty minutes of contraction significantly reduced muscle glycogen concentration in wild-type (49%) and transgenic (27%) mice, although transgenic mice retained 168.8 ± 20.5 μmol/g glycogen compared with 17.7 ± 2.6 μmol/g glycogen for wild-type mice. Muscle of transgenic and wild-type mice demonstrated similar pre- (3.6 ± 0.3 and 3.9 ± 0.6 μmol·g-1·h-1 for transgenic and wild-type, respectively) and postcontraction (7.9 ± 0.4 and 7.0 ± 0.4 μmol·g-1·h-1 for transgenic and wild-type, respectively) insulin-stimulated glucose uptakes. However, the [14C]glucose incorporated into glycogen was greater in noncontracted (151%) and postcontracted (157%) transgenic muscle vs. muscle of corresponding wild-type mice. These results indicate that glycogen synthase activity is not rate limiting for insulin-stimulated glucose uptake in skeletal muscle and that the inverse relationship between muscle glycogen and insulin-stimulated glucose uptake is an association, not a cause and effect relationship.

Effects of endurance exercise training on muscle glycogen accumulation in humans

1999 ◽  
Vol 87 (1) ◽  
pp. 222-226 ◽  
Author(s):  
Jeffrey S. Greiwe ◽  
Robert C. Hickner ◽  
Polly A. Hansen ◽  
Susan B. Racette ◽  
May M. Chen ◽  
...  
Keyword(s):  
Exercise Training ◽  
Endurance Exercise ◽  
Muscle Glycogen ◽  
Human Skeletal Muscle ◽  
Glycogen Synthase ◽  
Glycogen Accumulation ◽  
Glycogen Concentration ◽  
Endurance Exercise Training ◽  
Before And After ◽  
Muscle Glycogen Concentration

The purpose of this investigation was to determine whether endurance exercise training increases the ability of human skeletal muscle to accumulate glycogen after exercise. Subjects (4 women and 2 men, 31 ± 8 yr old) performed high-intensity stationary cycling 3 days/wk and continuous running 3 days/wk for 10 wk. Muscle glycogen concentration was measured after a glycogen-depleting exercise bout before and after endurance training. Muscle glycogen accumulation rate from 15 min to 6 h after exercise was twofold higher ( P < 0.05) in the trained than in the untrained state: 10.5 ± 0.2 and 4.5 ± 1.3 mmol ⋅ kg wet wt−1 ⋅ h−1, respectively. Muscle glycogen concentration was higher ( P < 0.05) in the trained than in the untrained state at 15 min, 6 h, and 48 h after exercise. Muscle GLUT-4 content after exercise was twofold higher ( P < 0.05) in the trained than in the untrained state (10.7 ± 1.2 and 4.7 ± 0.7 optical density units, respectively) and was correlated with muscle glycogen concentration 6 h after exercise ( r = 0.64, P < 0.05). Total glycogen synthase activity and the percentage of glycogen synthase I were not significantly different before and after training at 15 min, 6 h, and 48 h after exercise. We conclude that endurance exercise training enhances the capacity of human skeletal muscle to accumulate glycogen after glycogen-depleting exercise.

Muscle glycogen accumulation after endurance exercise in trained and untrained individuals

1997 ◽  
Vol 83 (3) ◽  
pp. 897-903 ◽  
Author(s):  
R. C. Hickner ◽  
J. S. Fisher ◽  
P. A. Hansen ◽  
S. B. Racette ◽  
C. M. Mier ◽  
...  
Keyword(s):  
Endurance Exercise ◽  
Muscle Glycogen ◽  
Plasma Insulin ◽  
Glycogen Synthase ◽  
Area Under The Curve ◽  
Accumulation Rates ◽  
Glycogen Accumulation ◽  
Endurance Exercise Training ◽  
Plasma Creatine Kinase ◽  
Muscle Glycogen Concentration

Hickner, R. C., J. S. Fisher, P. A. Hansen, S. B. Racette, C. M. Mier, M. J. Turner, and J. O. Holloszy. Muscle glycogen accumulation after endurance exercise in trained and untrained individuals. J. Appl. Physiol. 83(3): 897–903, 1997.—Muscle glycogen accumulation was determined in six trained cyclists (Trn) and six untrained subjects (UT) at 6 and either 48 or 72 h after 2 h of cycling exercise at ∼75% peak O2 uptake (V˙o 2 peak), which terminated with five 1-min sprints. Subjects ate 10 g carbohydrate ⋅ kg−1 ⋅ day−1for 48–72 h postexercise. Muscle glycogen accumulation averaged 71 ± 9 (SE) mmol/kg (Trn) and 31 ± 9 mmol/kg (UT) during the first 6 h postexercise ( P < 0.01) and 79 ± 22 mmol/kg (Trn) and 60 ± 9 mmol/kg (UT) between 6 and 48 or 72 h postexercise (not significant). Muscle glycogen concentration was 164 ± 21 mmol/kg (Trn) and 99 ± 16 mmol/kg (UT) 48–72 h postexercise ( P < 0.05). Muscle GLUT-4 content immediately postexercise was threefold higher in Trn than in UT ( P < 0.05) and correlated with glycogen accumulation rates ( r = 0.66, P < 0.05). Glycogen synthase in the active I form was 2.5 ± 0.5, 3.3 ± 0.5, and 1.0 ± 0.3 μmol ⋅ g−1 ⋅ min−1in Trn at 0, 6, and 48 or 72 h postexercise, respectively; corresponding values were 1.2 ± 0.3, 2.7 ± 0.5, and 1.6 ± 0.3 μmol ⋅ g−1 ⋅ min−1in UT ( P < 0.05 at 0 h). Plasma insulin and plasma C-peptide area under the curve were lower in Trn than in UT over the first 6 h postexercise ( P < 0.05). Plasma creatine kinase concentrations were 125 ± 25 IU/l (Trn) and 91 ± 9 IU/l (UT) preexercise and 112 ± 14 IU/l (Trn) and 144 ± 22 IU/l (UT; P < 0.05 vs. preexercise) at 48–72 h postexercise (normal: 30–200 IU/l). We conclude that endurance exercise training results in an increased ability to accumulate muscle glycogen after exercise.

Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis

2001 ◽  
Vol 280 (5) ◽  
pp. E712-E719 ◽  
Author(s):  
Patricia Iozzo ◽  
Thonchai Pratipanawatr ◽  
Hanno Pijl ◽  
Christoph Vogt ◽  
Vineeta Kumar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Muscle Glycogen ◽  
Healthy Subjects ◽  
Glycogen Synthase ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glycogen Concentration ◽  
Insulin Clamp ◽  
Mrna Content ◽  
Muscle Glycogen Concentration

Although chronic hyperinsulinemia has been shown to induce insulin resistance, the basic cellular mechanisms responsible for this phenomenon are unknown. The present study was performed 1) to determine the time-related effect of physiological hyperinsulinemia on glycogen synthase (GS) activity, hexokinase II (HKII) activity and mRNA content, and GLUT-4 protein in muscle from healthy subjects, and 2) to relate hyperinsulinemia-induced alterations in these parameters to changes in glucose metabolism in vivo. Twenty healthy subjects had a 240-min euglycemic insulin clamp study with muscle biopsies and then received a low-dose insulin infusion for 24 ( n = 6) or 72 h ( n = 14) (plasma insulin concentration = 121 ± 9 or 143 ± 25 pmol/l, respectively). During the baseline insulin clamp, GS fractional velocity (0.075 ± 0.008 to 0.229 ± 0.02, P < 0.01), HKII mRNA content (0.179 ± 0.034 to 0.354 ± 0.087, P < 0.05), and HKII activity (2.41 ± 0.63 to 3.35 ± 0.54 pmol · min−1 · ng−1, P < 0.05), as well as whole body glucose disposal and nonoxidative glucose disposal, increased. During the insulin clamp performed after 24 and 72 h of sustained physiological hyperinsulinemia, the ability of insulin to increase muscle GS fractional velocity, total body glucose disposal, and nonoxidative glucose disposal was impaired (all P < 0.01), whereas the effect of insulin on muscle HKII mRNA, HKII activity, GLUT-4 protein content, and whole body rates of glucose oxidation and glycolysis remained unchanged. Muscle glycogen concentration did not change [116 ± 28 vs. 126 ± 29 μmol/kg muscle, P = nonsignificant (NS)] and was not correlated with the change in nonoxidative glucose disposal ( r = 0.074, P = NS). In summary, modest chronic hyperinsulinemia may contribute directly (independent of change in muscle glycogen concentration) to the development of insulin resistance by its impact on the GS pathway.

Role of glycogen concentration and epinephrine on glucose uptake in rat epitrochlearis muscle

1997 ◽  
Vol 272 (4) ◽  
pp. E649-E655 ◽  
Author(s):  
J. Jensen ◽  
R. Aslesen ◽  
J. L. Ivy ◽  
O. Brors
Keyword(s):  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Similar Treatment ◽  
Glycogen Concentration ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
Tracer Amount ◽  
Muscle Glycogen Concentration ◽  
Basal Glucose Uptake

The effects of diet-manipulated variations in muscle glycogen concentration and epinephrine on glucose uptake were studied in epitrochlearis muscles from Wistar rats. Both basal and insulin-stimulated glucose uptake [measured with a tracer amount of 2-[1,2-3H(N)]deoxy-D-glucose] inversely correlated with initial glycogen concentration (glycogen concentration vs. basal glucose uptake: Spearman's rho = -0.76, n = 84, P < 0.000001; glycogen concentration vs. insulin-stimulated glucose uptake: Spearman's rho = -0.67, n = 44, P < 0.00001). Two fasting-refeeding procedures were used that resulted in differences in muscle glycogen concentrations, although with similar treatment for the last 48 h before the experiment. In the rats with the lower glycogen concentration, basal as well as insulin-stimulated glucose uptake was elevated. The muscle glycogen concentration had no effect on epinephrine-stimulated glycogenolysis. Epinephrine, however, was found to reduce basal glucose uptake in all groups. These results suggest that 1) the glycogen concentration participates in the regulation of both basal and insulin-stimulated glucose uptake in skeletal muscle, 2) the magnitude of epinephrine-stimulated glycogen breakdown is independent of the glycogen concentration, and 3) epinephrine inhibits basal glucose uptake at all glycogen concentrations.

Muscle glycogen concentrations in commercial consignments of Australian lamb measured on farm and post-slaughter after three different lairage periods

2005 ◽  
Vol 45 (5) ◽  
pp. 543 ◽  
Author(s):  
R. H. Jacob ◽  
D. W. Pethick ◽  
H. M. Chapman
Keyword(s):  
Western Australia ◽  
Muscle Glycogen ◽  
Glycogen Concentration ◽  
Age Class ◽  
Muscle Types ◽  
Carry Over ◽  
On Farm ◽  
Muscle Glycogen Concentration

The aim of this study was to gain an understanding of the distribution of glycogen concentrations and ultimate pH (pHu) in 2 different muscle types for lambs slaughtered under commercial conditions in Western Australia, and to compare muscle glycogen concentrations in lambs on farm and after slaughter. The study included 13 different consignments of prime lambs from a range of commercial scenarios. In each consignment, muscle glycogen concentration was measured in a group of lambs on farm and subsequently after slaughter in 3 different lairage groups. The lairage groups were: slaughter on arrival (no lairage), slaughter after 1 day, and slaughter after 2 days in lairage. Biopsies of M. semimembranosus and the M. semitendinosus were taken from live lambs on farm just before farm curfew before transport and from carcasses immediately after slaughter. There was a significant effect of consignment on muscle glycogen concentration. Muscle glycogen concentrations on farm were lower than 1 g/100 g in 4 consignments for the M. semimembranosus and 11 consignments for the M. semitendinosus. The cause of the differences between consignments was unclear as nutrition, genotype and age class were confounded between consignments. Glycogen concentrations were lower and meat pHu higher for sucker lamb compared with carry-over lamb consignments. However, lambs finished on grain-based feedlot rations had higher muscle glycogen concentrations than lambs finished on pasture and sucker lambs when finished on pastures only. Sucker lambs were only crossbred while carry-over lambs included crossbred and Merino genotypes. When data from different consignments were pooled and the effect of consignment was considered, there were no differences between muscle glycogen concentration measured on farm and muscle glycogen concentration measured after slaughter. However, there were differences between sample times within individual consignments. Glycogen concentration at slaughter was different from glycogen concentration on farm in more consignments for M. semitendinosus than M. semimembranosus, suggesting a difference between consignments for the effect caused by stress. Typically, the M. semimembranosus glycogen concentration at slaughter was lower than on farm in consignments consisting of Merino genotypes that had high muscle glycogen concentrations on farm. In the consignments in which lairage time had an effect on muscle glycogen concentration, the differences were small. In some consignments a difference occurred between lairage times for pHu without any difference occurring for muscle glycogen concentration.

Persistent increase in glucose uptake by rat skeletal muscle following exercise

1981 ◽  
Vol 241 (5) ◽  
pp. C200-C203 ◽  
Author(s):  
J. L. Ivy ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Synthesis ◽  
Exercise Stress ◽  
Rat Skeletal Muscle ◽  
Major Pathway ◽  
Glycogen Accumulation ◽  
Hindlimb Muscles ◽  
Muscle Glycogen Concentration

The effect of a bout of exercise on glucose uptake and glycogen synthesis in skeletal muscle was examined using a perfused rat hindlimb preparation. Rats were subjected to a bout of swimming. The exercise stress was moderate as reflected in a reduction of muscle glycogen concentration of only 50%. Glucose uptake and glycogen synthesis were measured in perfused hindlimb muscles for a 30-min period beginning approximately 60 min following the exercise. The rate of glucose uptake in the absence of insulin was 10-fold higher in hindlimbs of exercised animals than in the controls. The rate of glucose uptake was also higher in exercised than in control muscles in the presence of 50 microunits/ml or 10 mU/ml of insulin, but these differences were smaller than that found in the absence of insulin. Conversion to glycogen was the major pathway for disposal of the glucose taken up by muscle. The rate of glycogen accumulation in the exercised plantaris muscles was greater than in the control muscles both in the absence and presence of insulin.

Effect of endurance exercise training on muscle glycogen supercompensation in rats

1997 ◽  
Vol 82 (2) ◽  
pp. 711-715 ◽  
Author(s):  
Akira Nakatani ◽  
Dong-Ho Han ◽  
Polly A. Hansen ◽  
Lorraine A. Nolte ◽  
Helen H. Host ◽  
...  
Keyword(s):  
Exercise Training ◽  
Endurance Exercise ◽  
Muscle Glycogen ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Recovery Period ◽  
Chow Diet ◽  
Glycogen Accumulation ◽  
Transporter Protein ◽  
Endurance Exercise Training

Nakatani, Akira, Dong-Ho Han, Polly A. Hansen, Lorraine A. Nolte, Helen H. Host, Robert C. Hickner, and John O. Holloszy.Effect of endurance exercise training on muscle glycogen supercompensation in rats. J. Appl. Physiol. 82(2): 711–715, 1997.—The purpose of this study was to test the hypothesis that the rate and extent of glycogen supercompensation in skeletal muscle are increased by endurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for an additional 2 wk. Glycogen repletion was measured in trained and untrained rats after a glycogen-depleting bout of exercise. The rats were given a rodent chow diet plus 5% sucrose in their drinking water ad libitum during the recovery period. There were remarkable differences in both the rates of glycogen accumulation and the glycogen concentrations attained in the two groups. The concentration of glycogen in epitrochlearis muscle averaged 13.1 ± 0.9 mg/g wet wt in the untrained group and 31.7 ± 2.7 mg/g in the trained group ( P < 0.001) 24 h after the exercise. This difference could not be explained by a training effect on glycogen synthase. The training induced ∼50% increases in muscle GLUT-4 glucose transporter protein and in hexokinase activity in epitrochlearis muscles. We conclude that endurance exercise training results in increases in both the rate and magnitude of muscle glycogen supercompensation in rats.

Glucose transport rate and glycogen synthase activity both limit skeletal muscle glycogen accumulation

2002 ◽  
Vol 282 (6) ◽  
pp. E1214-E1221 ◽  
Author(s):  
Jonathan S. Fisher ◽  
Lorraine A. Nolte ◽  
Kentaro Kawanaka ◽  
Dong-Ho Han ◽  
Terry E. Jones ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Muscle Glycogen ◽  
Glycogen Synthase ◽  
Transport Rate ◽  
Prolonged Incubation ◽  
Glycogen Accumulation ◽  
Gf 109203X ◽  
Rate Limiting ◽  
Glycogen Synthase Activity

We varied rates of glucose transport and glycogen synthase I (GS-I) activity (%GS-I) in isolated rat epitrochlearis muscle to examine the role of each process in determining the rate of glycogen accumulation. %GS-I was maintained at or above the fasting basal range during 3 h of incubation with 36 mM glucose and 60 μU/ml insulin. Lithium (2 mM LiCl) added to insulin increased glucose transport rate and muscle glycogen content compared with insulin alone. The glycogen synthase kinase-3β inhibitor GF-109203x (GF; 10 μM) maintained %GS-I about twofold higher than insulin with or without lithium but did not increase glycogen accumulation. When %GS-I was lowered below the fasting range by prolonged incubation with 36 mM glucose and 2 mU/ml insulin, raising rates of glucose transport with bpV(phen) or of %GS-I with GF produced additive increases in glycogen concentration. Phosphorylase activity was unaffected by GF or bpV(phen). In muscles of fed animals, %GS-I was ∼30% lower than in those of fasted rats, and insulin-stimulated glycogen accumulation did not occur unless %GS-I was raised with GF. We conclude that the rate of glucose transport is rate limiting for glycogen accumulation unless %GS-I is below the fasting range, in which case both glucose transport rate and GS activity can limit glycogen accumulation.

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