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
Abbreviations: BMI=Body Mass Index, ERK=Extracellular Regulated signal Kinase, GS=Glycogen Synthase, GSK=Glycogen Synthase Kinase, T2DM=type 2 Diabetes Mellitus, ↑=significant increases due to factor/manipulation, ↓=significant decreases due to factor/manipulation.
Table 3: Factors negatively impacting GS regulation in studies using human materials.