| Factor/Manipulation |
Participants/Model System |
Treatment/Manipulation; Duration |
Findings |
Proposed Mechanisms |
Citation |
| PPP1R3A Mutation |
Wild-type and mutant (premature stop mutation in PPP1R3A) mice Parent strain- Chimeric mice cross-bed with C57BL/6J mice (examined muscle not specified) |
Tissues collected during ad libitum. Age used not described. |
↓ Glycogen content and GS activity
↑ GP activity |
The reduction in GS activity was most likely due to the inability of PP1 to colocalize with GS and to bind to glycogen. |
58 |
| GS-PMO |
C57BL/6+GAA-/- mice
(examined quadriceps muscle) |
GS-PMO administered at 15 or 30 mg/kg bodyweight by tail vein injection once every 2 weeks for a total of 12 weeks, muscle isolated 2 weeks after stopping treatment |
↓ Glycogen content, GS activity, GS mRNA expression, and GS protein level |
GS-PMO forces exon skipping in the processing of Gys1 mRNA, leading to a premature termination codon. |
61 |
| AICAR |
Male Sprague-Dawley rats
(examined epitrochlearis muscles)
Male Albino-Wistar rats
(examined soleus and epitrochlearis muscles) |
AICAR (2 mM) and insulin (1 µM) - 40 minutes
AICAR (2 mM) and insulin (100 nM)- 45, 60 and 75 min (preincubated with AICAR 30 min before insulin added) |
↓ basal and insulin-stimulated GS activity
↓ insulin-stimulated glycogen synthesis and glycogen content (soleus muscle)
↑ GS phosphorylation at Ser641 (45 min, soleus muscle) |
AICAR treatment favors an increase in glycolytic flux instead of glycogen synthesis.
AICAR treatment led to a time-dependent reduction in Akt phosphorylation at Thr308 and activation of GSK-3α/β. |
62
63 |
| AICAR |
Male Sprague-Dawley rats
(examined epitrochlearis muscles)
Male Albino-Wistar rats
(examined soleus and epitrochlearis muscles) |
AICAR (2 mM) and insulin (1µM) - 40 min
AICAR (2 mM) and insulin (100 nM)- 45, 60,and 75 min (preincubated with AICAR 30 min before insulin added) |
↓ basal and insulin-stimulated GS activity
↓ insulin-stimulated glycogen synthesis and glycogen content (soleus muscle)
↑ GS phosphorylation at Ser641 (45 minutes, soleus muscle) |
AICAR treatment favors an increase in glycolytic flux instead of glycogen synthesis.
AICAR treatment led to a time-dependent reduction in Akt phosphorylation at Thr308 and activation of GSK-3α/β. |
62
63 |
| Adrenaline |
C57BL/6 J mice (examined EDL muscle)
Male Wistar rats (examined soleus muscle)
Wild-type and null GM allele (deletion encompassing 1st exon encoding PP1) mice
Parent strain: C57BL/6 mice |
Adrenaline (10µM)- 40 min
Adrenaline (10µM) - 30 min
Adrenaline (0.5 mg/g) for 15 min, insulin (150 mU/g) for 20 min or saline intraperitoneal injections |
↓ GS activity
↑ GS phosphorylation at Ser8/11, GP activity, and GP phosphorylation at Ser15
↑ GS (Ser645/649/653/657) phosphorylation
↓ GS activity
↑ GP activity |
Adrenaline impairs dephosphorylation of GS atSer8/11 while promoting GP phosphorylation at Ser15.
Adrenaline impairs dephosphorylation of GS atSer645/649/653/657 most likely through PKA signaling pathway, which may also lead to decreases in PP1 activity.
Adrenaline’s effects may be attributed to decrease in PP1 activity and/or increase in phosphorylase kinase activity. |
64
67
68 |
| (examined hind limb muscles) |
| Age |
Male Fischer 344 rats (examined soleus and tibialis anterior muscles) |
Old (24 months) rats compared to young (6 months) rats maintained ad libitum or calorie restricted |
↓ GS and GP activity and GS protein levels (soleus)
↑ GS phosphorylation at Ser640 (soleus) |
Aging negatively affects GS and GP activity in soleus muscle, which may be associated with impairment of dephosphorylation of GS at Ser640. |
70 |
| Oxidant Stress |
Female lean Zucker rats (examined soleus muscle) |
Isolated muscle from 9-10 week old rats incubated for 2 h in the absence or presence of 100 mU/mL glucose oxidase, without or with 5 mU/ml insulin. |
↓ insulin-stimulated GS activity and glycogen synthesis |
Oxidant stress was found to be associated with decreased phosphorylation of insulin receptor, Akt at Ser473, and GSK-3b at Ser9. |
50 |
| GM null allele |
Wild-type and null GM allele (deletion encompassing 1st exon encoding PP1) mice
Parent strain- C57BL/6 mice
(examined hind limb muscles) |
Adrenaline (0.5 mg/g) for 15 min, insulin (150 mU/g) for 20 min, or saline via intraperitoneal injection |
↓ insulin-stimulated GS activity (null GM mice)
↑ GS phosphorylation at Ser7/640/644 and GP phosphorylation at Ser14 (null GM mice) |
Decreased PP1 activity allows for GS and GP phosphorylation which may also be attributed to increases in phosphorylase kinase activity. |
68 |
| Dexamethasone |
Male Sprague -Dawley rats (examined gastrocnemius muscle) |
4 groups: saline, 10% sucrose drinking solution, dexamethasone (1 mg), and dexamethasone+sucrose- 7 days. |
↑ Glycogen content (dexamethasone alone)
↓ GS activity (dexamethasone and dexamethasone+sucrose) |
Dexamethasone may regulate GSK-3 and/or CAMKII activity. |
75 |
