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Published on: June 25, 2017
The cGMP-inhibitable phosphodiesterase modulates glucose transport activation by insulin
J W Eriksson1, C Wesslau, U Smith
1Department of Medicine, University of Göteborg, Sahlgren's Hospital, Sweden.
Abstract:
To assess the role of the cGMP-inhibitable phosphodiesterase (cGI-PDE) in the action of insulin on glucose transport, adipocytes from young, lean rats were preincubated for 20 min at 37 degrees C with and without OPC 3911, a specific inhibitor of cGI-PDE, and 3-O-methylglucose uptake was measured. Insulin-stimulated glucose transport was impaired by OPC 3911 (approximately 15%) and this impairment became more pronounced in the presence of the degradable cAMP-analogue 8-bromo-cAMP (approximately 45%). This analogue alone did not significantly decrease glucose transport. Furthermore, insulin sensitivity was impaired by the combination of OPC 3911 and 8-bromo-cAMP. Maximal insulin-stimulated glucose transport in adipocytes from aging, obese rats was affected similarly by OPC 3911 and 8-bromo-cAMP, suggesting that cGI-PDE activity is not markedly altered in this insulin-resistant state. In conclusion, cGI-PDE exerts a modulating effect on the stimulatory action of insulin on glucose transport. This effect is particularly pronounced when the cellular cAMP levels are elevated.
Insights
The cGMP-inhibitable phosphodiesterase (cGI-PDE) modulates insulin
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Research
Background:
- Insulin is crucial for glucose uptake in adipocytes.
- The role of cGMP-inhibitable phosphodiesterase (cGI-PDE) in insulin signaling is not fully understood.
- Elevated cAMP levels can influence insulin sensitivity.
Purpose of the Study:
- To investigate the role of cGI-PDE in insulin-stimulated glucose transport.
- To determine if cGI-PDE inhibition affects insulin sensitivity, particularly under conditions of elevated cAMP.
- To examine cGI-PDE activity in insulin-resistant states.
Main Methods:
- Adipocytes from young, lean rats were used.
- Cells were treated with OPC 3911, a specific cGI-PDE inhibitor.
- 3-O-methylglucose uptake was measured with and without insulin stimulation.
- The effects of OPC 3911 were assessed alone and in combination with 8-bromo-cAMP, a cAMP analogue.
Main Results:
- OPC 3911 impaired insulin-stimulated glucose transport by approximately 15%.
- This impairment was significantly greater (approximately 45%) when combined with 8-bromo-cAMP.
- Insulin sensitivity was reduced by the combination of OPC 3911 and 8-bromo-cAMP.
- In aging, obese rats, maximal insulin-stimulated glucose transport was similarly affected by OPC 3911 and 8-bromo-cAMP, suggesting no significant change in cGI-PDE activity in this insulin-resistant state.
Conclusions:
- cGMP-inhibitable phosphodiesterase (cGI-PDE) plays a modulating role in insulin's effect on glucose transport.
- This modulation is more pronounced when cellular cyclic adenosine monophosphate (cAMP) levels are elevated.
- The cGI-PDE pathway does not appear to be significantly altered in the insulin resistance associated with aging and obesity.
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