| Factor/Manipulation |
Participants/Model System |
Treatment/Manipulation; Duration |
Findings |
Proposed Mechanisms |
Citation |
| Pro-longed insulin treatment |
Human skeletal muscle cells |
Insulin (300 nM)- 5 h |
↑ Glycogen content
↓ GS activity and glycogen synthesis rate |
Pro-longed insulin treatment could result in a negative feedback mechanism on insulin signaling pathway |
65 |
| Adrenaline |
Male and female healthy subjects (examined tibialis anterior muscle) |
Adrenaline (0.05 µg/kg/minute) or saline infusion for 240 minutes. Euglycaemic-hyperinsulinemic clamp for 120-240 minutes |
↓ insulin-stimulated Glycogen synthesis, GS activity, and dephosphorylation of GS atSer641 |
Adrenaline blocks insulin-mediated GS activation most likely due to preventing dephosphorylation of GSat Ser641. |
66 |
| T2DM |
Obese male subjects with or without T2DM (examined vastuslateralis muscle) |
Exercise on a cycle ergometer for 60 min at an intensity (~70% VO2max) followed with 1-3 h of recovery period |
↓ GS activity
↑ GS P-Ser7/10 during recovery period (diabetic vs. obese) |
Muscle GS phosphorylation regulation in T2DM is impaired in response to recovery from exercise. |
30 |
| Obese subjects with or without T2DM, and lean non-diabetic subjects (examined vastuslateralis muscle) |
Following overnight fast, lean and obese controls underwent a euglycemic-hyperinsulinemic clamp (4h) with tracer glucose and combined with indirect calorimetry; diabetic patients were clamped twice with either a euglycemic or an isoglycaemic-hyperinsulinaemic clamp (fixing glucose at the fasting glucose level) separated by 4-6 weeks |
↓ insulin-stimulated GS activity during euglycemia
↓ insulin-stimulated dephosphorylation of GS atSer7/10 during euglycemia and hyperglycemia |
T2DM impairs insulin-stimulated glycogen synthesis involving Akt phosphorylation at Ser473 and Thr308, and dephosphorylation of GS at Ser7/10. |
69 |
| PCOS |
Obese women with or without PCOS (examined vastuslateralis muscle) |
Euglycemic-hyperinsulinemic clamp performed for 3 h. |
↓ insulin-stimulated GS activity and dephosphorylation of GS at Ser7/10 (PCOS vs. control) |
PCOS decreased the insulin-mediated dephosphorylation of GS at Ser7/10. |
57 |
| Physical Inactivity |
Healthy male subjects (examined vastuslateralis muscle) |
Bed rest (all transport of subjects took place in wheelchairs)- 7 days |
↓ GS activity
↑ GS phosphorylation at Ser7/10 |
Physical inactivity/bed rest impairs muscle insulin signaling and dephosphorylation of GS atSer7/10. |
71 |
| High glucose+angiotensin |
Human skeletal muscle cells |
Muscle cells were incubated with or without 25 mM glucose for 24 h.
Angiotensin treatment (1µM) - 20 min |
↓ GS activity
↑ GS phosphorylation at Ser640/641 |
Angiotensin reduced ERK½ phosphorylation at Thr202/Tyr204 and impaired dephosphorylation of GS at Ser640/641. |
72 |
