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Published on: June 25, 2017
CDK5 inhibition improves glucose uptake in insulin-resistant neuronal cells via ERK1/2 pathway
Kapil Manglani1, Chinmoy S Dey1
1Kusuma School of Biological Sciences, Indian Institute of Technology, Hauz Khas, New Delhi, India.
Abstract:
Role of CDK5 and its inhibition in various neuronal processes and functions are well established. However, role of CDK5 and its inhibition in neuronal insulin-signaling and-resistance is not yet explored. In the present study, we investigated the effect of CDK5 inhibition in neuronal insulin signaling, specifically insulin-stimulated glucose uptake. CDK5 expression in neuro-2a cells was increased under insulin-resistant state, developed by chronic treatment of insulin, confirming the crucial role of CDK5 in insulin resistance in neuronal cells. However, whether increased expression of CDK5 in hyperinsulinemia-mediated insulin-resistant conditions is a cause or a consequence, is still an unanswered question. We showed that CDK5 inhibition did not affect basal insulin signaling; however, insulin-stimulated glucose uptake enhanced in insulin-resistant cells. Moreover, CDK5 inhibition could improve glucose uptake, the ultimate outcome of insulin signaling, in insulin-resistant neuro-2a cells. We first time showed that CDK5 inhibition by roscovitine could ameliorate insulin resistance and increase glucose uptake in neuronal cells via ERK1/2 pathway. Our study provides intriguing insights about the effect of CDK5 inhibition on neuronal insulin resistance and opens up a new paradigm to develop new therapeutic strategies for neuronal insulin resistance and associated pathophysiological conditions.
Insights
Inhibiting CDK5 enhances glucose uptake in insulin-resistant neuronal cells. This finding offers a new therapeutic approach for addressing neuronal insulin resistance and related conditions.
Area of Science:
- Neuroscience
- Cell Biology
- Metabolism
Background:
- Cyclin-dependent kinase 5 (CDK5) plays a known role in neuronal functions.
- The involvement of CDK5 in neuronal insulin signaling and insulin resistance remains unexplored.
Purpose of the Study:
- To investigate the effect of CDK5 inhibition on neuronal insulin signaling, focusing on insulin-stimulated glucose uptake.
- To explore the potential of CDK5 inhibition as a therapeutic strategy for neuronal insulin resistance.
Main Methods:
- Developed an insulin-resistant neuro-2a cell model using chronic insulin treatment.
- Assessed CDK5 expression levels in insulin-resistant cells.
- Investigated the impact of CDK5 inhibition (using roscovitine) on basal and insulin-stimulated glucose uptake.
- Examined the role of the ERK1/2 pathway in mediating the effects of CDK5 inhibition.
Main Results:
- CDK5 expression increased in insulin-resistant neuro-2a cells.
- CDK5 inhibition did not affect basal insulin signaling but enhanced insulin-stimulated glucose uptake in insulin-resistant cells.
- CDK5 inhibition ameliorated insulin resistance and increased glucose uptake via the ERK1/2 pathway.
Conclusions:
- CDK5 plays a significant role in neuronal insulin resistance.
- Inhibiting CDK5 can improve glucose uptake in insulin-resistant neuronal cells.
- CDK5 inhibition presents a novel therapeutic avenue for neuronal insulin resistance and associated disorders.
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