Factor/Manipulation |
Participants/Model System |
Treatment/Manipulation; Duration |
Findings |
Proposed Mechanisms |
Citation |
Physical Activity/Muscle Contraction |
Male Wistar rats (examined epitrochlearis muscle) |
Muscles were kept rested or contracted electrically while incubating with or without insulin (10 mU/mL) for 30 minutes |
↑ insulin-stimulated GS activity
↓ GS phosphorylation at Ser645/649/653/657 |
Muscle contraction can increase AMPKa phosphorylation at Thr172 and decrease GS phosphorylation at Ser645/649/653/657. |
29 |
Female Sprague Dawley rats (examined triceps and epitrochlearis muscles) |
Two groups- rats in the untrained group were housed individually in plastic cages and rats in the trained group were housed in wheel cages. Trained either for 1 week, 4 weeks, or 7 weeks. |
↑ Glycogen content after 4 and 7 weeks (triceps)
↑ GS activity after 4 and 7 weeks (triceps) |
Physical activity may enhance insulin sensitivity and PP1 activity. |
36 |
Female white New Zealand rabbits (examined tibialis anterior muscle) |
Electrostimulations to mimic contraction were applied for 1 hour or 24 hours. After stimulation, animals were allowed to recover for 0, 1, 6, 12, or 24 hours. |
↑ Glycogen content during a 6-hour recovery phase after a 24-hour stimulation↑ GS activity↓ GP activity and GS (Ser640) phosphorylation |
Prolonged muscle contraction can increase GS activity by decreasing GS phosphorylation at Ser640 while decreasing GP activity. |
37 |
GLUT4 Repression |
Wild-type and muscle-specific GLUT4-knockout mice
Parent strains - 129SV and
C57Bl/6J mice (examined soleus, gastrocnemius, and tibialis anterior muscles) |
Transgenic mice with muscle-specific GLUT4 knockout. Electrical stimulation to mimic contraction. Mice were studied at 4 to 12 months of age. |
↑ Glycogen content
↑ GS activity (tibialis anterior and gastrocnemius)
↓ GS phosphorylation at Ser641 (gastrocnemius)
↓ GP activity (tibialis anterior and gastrocnemius) |
Decreased muscle glucose transport was associated with decreasing GS phosphorylation at Ser641 and GP activity. |
38 |
AMPK
overexpression |
Wild-type and transgenic mice with AMPKγ3 or AMPKγ3 R225Q mutant over-expressions
Parent strain- FVB mice (examined EDL, soleus, gastrocnemius, and tibialis anterior muscles) |
Mice were compared at 8 to 10 weeks of age. |
↑ Glycogen content (both transgenic models; EDL, gastrocnemius,
and tibialis anterior)
↑ GS activity (both transgenic models in presence of G6P; gastrocnemius)
↓ GP activity (wild-type AMPKγ3 mice; gastrocnemius) |
Mechanism not described in detail, however, postulated that AMPKg could alter the function of the AMPKb subunit’s glycogen-binding domain in stimulating the activity of the glycogen debranching enzyme. |
39 |
AMPK
overexpression |
Wild-type and transgenic mice with AMPKγ3 or AMPKγ3 R225Q mutant overexpressions
Parent strain- FVB mice (examined EDL, soleus, gastrocnemius, and tibialis anterior muscles) |
Mice were compared at 8 to 10 weeks of age. |
↑ Glycogen content (both transgenic models; EDL, gastrocnemius,
and tibialis anterior)
↑ GS activity (both transgenic models in presence of G6P; gastrocnemius)
↓ GP activity (wild-type AMPKγ3 mice; gastrocnemius) |
Mechanism not described in detail, however, postulated that AMPKγ could alter the function of the AMPKβ subunit’s glycogen-binding domain in stimulating the activity of the glycogen debranching enzyme. |
39 |
Wild-type and AMPK overexpressing mice
(examined EDL, soleus, quadriceps, gastrocnemius, and tibialis anterior muscles) |
Mice were compared at 9 to 12 weeks of age. |
↑ Glycogen content (quadriceps, gastrocnemius,
and tibialis anterior)
↑ GS activity (gastrocnemius) |
With AMPKγ overexpression, there was reduction of G6P content which may result from increased G6P utilization and glycogen synthesis. |
40 |
SKIP repression |
Mouse C2C12 muscle cells |
Transfection of cultured C2C12 cells with siRNA against SKIP gene for 48 hours. Insulin (10 and 100 nM) for 30 minutes. |
↑ insulin-stimulated glycogen synthesis and dephosphorylation of GS at Ser641 |
SKIP negatively regulates the insulin-signaling pathway. Repression of SKIP allows for insulin-stimulated glycogen synthesis. |
49 |
Oxidant Stress |
Female lean Zucker rats at 9-10 weeks of age (examined soleus muscle) |
Isolated muscle incubated for 2 hours in the absence or presence of 100 mU/mL glucose oxidase without or with 5 mU/ml insulin |
↑ basal glycogen synthesis and GS activity |
Oxidant stress increased phosphorylation of insulin receptor, Akt at Ser473, and GSK-3β at Ser9.xdfc |
50 |
Whey Protein Hydrolysates |
Male ddY mice (examined gastrocnemius muscle) |
Mice fed 1 of 3 test diets for 5 weeks using AIN-93 protocol: control diet, control+39.550 g/kg of whey amino acids, control+50.00 g/kg of whey protein hydrolysates. |
↑ Glycogen content (whey protein hydrolysates>whey amino acids>control)
↑ GS mRNA expression and GS protein level (whey protein hydrolysates)
↓ GS phosphorylation at Ser641 (whey protein hydrolysates) |
Consumption of Whey protein decreases GS phosphorylation at Ser641 and could decrease 6-phosphofructokinase (regulatory glycolytic enzyme) activity to increase GS and glycogen content. |
52 |
Linoleate |
Rat L6 skeletal muscle cells |
Differentiating myotubes pre-treated for 16 h with 1 mMlinoleate in the absence or presence of insulin (100 nM) for 1 h. |
↑ basal and insulin -stimulated GS protein level (insoluble fraction) |
GS was sequestered from activation by insulin treatment due to lipid treatment. |
53 |
OA |
Control and streptozotocin-induced diabetic male Sprague-Dawley rats (examined hindquarter muscle) |
Rats were treated with insulin (4 IU/kg), OA (80 mg/kg), or the combination of OA+insulin in acute (60 minutes) and sub-chronic (14 days) studies. |
↑ GS activity after insulin+OA in diabetic group |
OA enhances insulin signaling pathway including phosphorylation of Akt at Ser473 |
56 |
TFE3 |
Control and transgenic mice expressing TFE3
Parent strain-C57Bl/6J mice
(examined gastrocnemius quadriceps, tibialis anterior muscle) |
Transgenic mice developed to muscle-specifically express TFE3. Mice used at 2 to 3 months of age. |
↑ Glycogen content in gastrocnemius and quadriceps
↑ GS mRNA expression in gastrocnemius |
TFE3 may be involved in increasing glucose uptake and substrate availability for GS. |
51 |