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Updated: Sep 21, 2026

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
A peroxovanadium compound stimulates muscle glucose transport as powerfully as insulin and contractions combined
Lorraine A Nolte1, Dong-Ho Han, Polly A Hansen
1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Abstract:
Stimulation of glucose transport by insulin involves tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRSs). Peroxovanadates inhibit tyrosine phosphatases, also resulting in tyrosine phosphorylation of the IRSs. Muscle contractions stimulate glucose transport by a mechanism independent of the insulin-signaling pathway. We found that the peroxovanadate compound bis-peroxovanadium,1,10-phenanthrolene [bpV(phen)] stimulates glucose transport to the same extent as the additive effects of maximal insulin and contraction stimuli. Translocation of GLUT4 to the cell surface mediates stimulation of glucose transport. There is evidence suggesting there are separate insulin- and contraction-stimulated pools of GLUT4-containing vesicles. We tested the hypothesis that bpV(phen) stimulates both the insulin- and the contraction-activated pathways. Stimulation of glucose transport and GLUT4 translocation by bpV(phen) was completely blocked by the phosphatidylinositol 3-kinase (PI 3-K) inhibitors wortmannin and LY294002. The combined effect of bpV(phen) and contractions was no greater than that of bpV(phen) alone. Activation of the IRS-PI 3-K signaling pathway was much greater with bpV(phen) than with insulin. Our results suggest that the GLUT4 vesicles that are normally translocated in response to contractions but not insulin can respond to the signal generated via the IRS-PI 3-K pathway if it is sufficiently powerful.
Insights
A novel compound, bis-peroxovanadium,1,10-phenanthrolene (bpV(phen)), significantly boosts glucose transport and GLUT4 translocation, mimicking maximal insulin and contraction effects. This suggests a powerful IRS-PI 3-K pathway activation can engage contraction-specific GLUT4 vesicles.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Regulation
Background:
- Insulin signaling, involving tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRSs), stimulates glucose transport.
- Muscle contractions independently stimulate glucose transport, suggesting distinct signaling pathways.
- Peroxovanadates, like bis-peroxovanadium,1,10-phenanthrolene (bpV(phen)), inhibit tyrosine phosphatases, enhancing IRS tyrosine phosphorylation.
Purpose of the Study:
- To investigate the effect of bpV(phen) on glucose transport and GLUT4 translocation.
- To determine if bpV(phen) activates both insulin- and contraction-stimulated pathways.
- To elucidate the role of the IRS-PI 3-K signaling pathway in bpV(phen)-mediated glucose uptake.
Main Methods:
- Treatment of cells with bpV(phen), insulin, and/or muscle contractions.
- Assessment of glucose transport and GLUT4 translocation.
- Inhibition of phosphatidylinositol 3-kinase (PI 3-K) using wortmannin and LY294002.
- Measurement of IRS-PI 3-K pathway activation.
Main Results:
- bpV(phen) stimulated glucose transport and GLUT4 translocation comparable to maximal insulin and contraction.
- bpV(phen)-induced effects were completely blocked by PI 3-K inhibitors.
- The combined effect of bpV(phen) and contractions did not exceed bpV(phen) alone.
- IRS-PI 3-K pathway activation was significantly higher with bpV(phen) than with insulin.
Conclusions:
- bpV(phen) powerfully activates the IRS-PI 3-K signaling pathway.
- This potent activation allows GLUT4 vesicles, typically responsive to contractions, to be translocated.
- The findings highlight the potential of targeting the IRS-PI 3-K pathway to enhance glucose uptake, particularly in conditions where insulin signaling is impaired.
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