| Factor/Manipulation |
Participants/Model System |
Treatment/Manipulation; Duration |
Findings |
Proposed Mechanisms |
Citation |
| Physical Activity/Muscle Contraction |
Obese subjects with or without T2DM (examined vastuslateralis muscle) |
On a cycle ergometer for 60 minutes at an intensity (~70% VO2max) followed with 1-3 hour of recovery period |
↑ GS activity
↑ GS phosphorylation at Ser7/10/640/644 |
Exercise increases substrate affinity and decreases GSK-3b activity. |
30 |
| |
Lean and obese subjects with normal glucose tolerance, obese subjects with T2DM (examined vastuslateralis muscle) |
On a cycle ergometer for 40 minutes at an intensity (~70% VO2max) |
↑ Glycogen content and GS phosphorylation at Ser7/641/645/649/653/657 |
Exercise increases GS affinity for UDP-glucose and decreases GS phosphorylation at Ser7/641/645/649/653/657. |
31 |
| |
Obese subjects with or without T2DM (examined vastuslateralis muscle) |
On cycle ergometer with four to five sessions of 20 to 35 min per week at an average intensity (~65% VO2max) - 10 weeks |
↑ GS activity and GS protein level |
Exercise can increase TBC1D4 signaling and influence key insulin-signaling protein levels. |
32 |
| |
Healthy, elderly male subjects (examined vastuslateralis muscle) |
On cycle ergometers twice per week, strength and mobility training once per week and a 5 km walk once a week. 8 weeks |
↑ Glycogen content and GS protein level↑ GS phosphorylation at Ser7/10/640 |
Exercise enhances glucose uptake and decreases GS (Ser7/10/640) phosphorylation. |
33 |
| |
Middle-aged sedentary or regularly active subjects (examined vastuslateralis muscle) |
Male subjects who performed endurance training (running and cycling) must have done so for years previous to study. Duration: 4 to 7 days between screening day and experimental (biopsy) day |
↑ GS protein level |
Mechanism not described in detail, however, having a high VO2max may influence insulin sensitivity in muscle. |
34 |
| Calorie Restriction+Physical Activity |
Older, overweight/obese insulin-resistant subjects (examined vastuslateralismuscle) |
Aerobic exercise training (treadmill at 50-70% VO2max for 20 to 50 minutes) +weight loss (restrict intake by 500 calories/day).6 months |
↑ GS activity (vs. baseline) |
Calorie restriction+physical activity may enhance whole-body insulin sensitivity. |
28 |
| Healthy, overweight, or obese post-menopausal women with normal or impaired glucose tolerance (examined vastuslateralis muscle) |
Women exercised at >85% heart rate reserve for 45 minutes, 3x per week and/or were instructed to reduce their caloric intake by 500 kcal/day.6 months |
↑ GS activity (in women with impaired glucose tolerance who exercised and restricted calories vs. restricted calories alone) |
Calorie restriction+physical activity may enhance whole-body insulin sensitivity. |
35 |
| GSK-3α Repression |
Human skeletal muscle cells isolated from nondiabetic subjects (biopsy samples of the vastuslateralis) |
Antisense oligo against GSK-3a were used for 6 hours to knockdown expression in differentiating cells. Insulin (33 nM) for 30 minutes. |
↑ insulin-stimulated GS fractional velocity |
GSK-3a repression may enhance insulin actions while overexpression can lead to insulin signaling impairment. |
41 |
| GSK-3β Repression |
Human skeletal muscle cells obtained from nondiabetic subjects (biopsy samples of the vastuslateralis) |
Transfection of cultured muscle cells with siRNA against GSK-3b for 4 hours. Insulin (33 nM) for 30 min. |
↑ basal and insulin-stimulated GS fractional velocity |
GSK-3b expression can affect GS activity in both basal and insulin-stimulated state, with GSK-3b repression allowing for activation of GS. |
43 |
| IL-6 |
Human skeletal muscle cells obtained from nondiabetic subjects (biopsy samples of rectus abdominus) |
IL-6 (5, 25, or 100 ng/ml).treatment for 20 min, 3 h, or 8 days |
↑ Glycogen synthesis (IL-6 ≥ 5 ng/mL)↑ GS mRNA expression (IL-6 25 ng/mL, 8 days) |
IL-6 increases glycogen synthesis via a PI3-kinase-dependent mechanism. |
47 |
| Adiponectin |
Lean subjects, obese subjects with or without T2DM (examined vastuslateralis muscle) |
Euglycemic -hyperinsulinemic clamp performed for 4 h |
↑ insulin-stimulated GS fractional velocity (positive association with plasma adiponectin levels) |
Plasma adiponectin may improve the ability to switch from lipid to glucose oxidation, and enhance muscle insulin sensitivity. |
48 |
| Pioglitazone |
Obese women with PCOS (examined vastuslateralis muscle) |
Euglycemic-hyperinsulinemic clamp performed for 3 hours. Treatment with either pioglitazone (30 mg) or placebo once daily- 16 weeks |
↑ insulin -stimulated GS activity and dephosphorylation of GS atSer7/640/644 |
Pioglitazone enhances insulin sensitivity and GS activity by promoting insulin-mediated dephosphorylation of GS at Ser7/640/644. |
57 |
