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Vanadate stimulation of 2-deoxyglucose transport is not mediated by PI 3-kinase in human skeletal muscle
R N Cortright1, J L Azevedo, M S Hickey
1Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858-4354, USA.
Abstract:
Glucose transport in mammalian skeletal muscle is stimulated by insulin, hypoxia and tyrosine protein phosphatase inhibitors such as vanadate. However, it is unknown whether the vanadate signaling mechanism shares a common or separate pathway with insulin or hypoxia. Therefore, experiments were conducted on incubated human muscle strips to compare the effects of vanadate with insulin and hypoxia stimulated 2-deoxyglucose transport (2-DOG). We also used the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin to examine whether PI 3-kinase is a common step by which each stimulate glucose transport. Results demonstrate that whereas the effects of vanadate and hypoxia were additive with insulin stimulated glucose transport, the effect of vanadate plus hypoxia was not. In addition, wortmannin significantly (P < 0.05) reduced insulin but not vanadate or hypoxia stimulated 2-DOG transport. Moreover, PI 3-kinase activity was significantly elevated (P < 0.05) in the presence of insulin but not vanadate. In conclusion, these data suggest that vanadate and hypoxia stimulate glucose transport via a similar signaling pathway which is distinct from insulin and that the vanadate signaling pathway is not mediated by PI 3-kinase in human skeletal muscle.
Insights
Vanadate and hypoxia stimulate glucose transport in human muscle via a pathway separate from insulin. This vanadate signaling mechanism does not involve phosphatidylinositol 3-kinase, unlike insulin-stimulated transport.
Area of Science:
- Cellular Physiology
- Molecular Biology
- Metabolic Regulation
Background:
- Insulin, hypoxia, and vanadate stimulate glucose transport in skeletal muscle.
- The signaling pathways for vanadate, insulin, and hypoxia in glucose transport are not fully understood.
- Investigating shared or distinct pathways is crucial for understanding muscle glucose uptake regulation.
Purpose of the Study:
- To compare the signaling mechanisms of vanadate, insulin, and hypoxia on glucose transport in human skeletal muscle.
- To determine if phosphatidylinositol 3-kinase (PI 3-kinase) is a common mediator for these stimuli.
- To elucidate the distinct pathways involved in vanadate and hypoxia-stimulated glucose uptake.
Main Methods:
- Incubated human muscle strips were used to measure 2-deoxyglucose transport (2-DOG).
- Experiments compared the effects of vanadate, insulin, and hypoxia, individually and in combination.
- The role of PI 3-kinase was assessed using the inhibitor wortmannin and by measuring PI 3-kinase activity.
Main Results:
- Vanadate and hypoxia effects were additive with insulin, but vanadate plus hypoxia effects were not.
- Wortmannin inhibited insulin-stimulated 2-DOG transport but not that stimulated by vanadate or hypoxia.
- PI 3-kinase activity increased with insulin but not with vanadate.
Conclusions:
- Vanadate and hypoxia utilize a common signaling pathway for glucose transport that is distinct from the insulin pathway.
- The vanadate signaling pathway in human skeletal muscle does not appear to be mediated by PI 3-kinase.
- These findings differentiate the molecular mechanisms regulating glucose uptake in skeletal muscle.