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Protein Kinase C Attenuates Insulin Signalling Cascade in Insulin-Sensitive and Insulin-Resistant Neuro-2a Cells

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Abstract

Protein kinase C (PKC) family of enzymes is known to be a feedback regulator of insulin signalling pathway in peripheral insulin-responsive tissues. Insulin signalling is reported to be required for maintaining cognitive abilities in brain. PKCs are involved in innumerable neuronal processes including differentiation, apoptosis, survival, maintaining synaptic plasticity, long-term potentiation and memory formation. In the present study, we made an attempt to elucidate the role of PKC, if any, in regulating insulin signalling and insulin resistance in Neuro-2a (N2a) cells in vitro. We show that phorbol 12-myristate 13-acetate (PMA) -activated PKC inhibited Akt activation in neuronal cell, N2a. In the process of inhibiting Akt, PMA-activated PKC decreased downstream insulin signalling proteins like Akt substrate 160 kDa (AS160) and glycogen synthase kinase (GSK3β), followed by a decrease of glucose uptake in N2a cells. PKC activation caused insulin resistance in N2a cells and worsened the resistant state of already insulin-resistant cells. Hence, our study demonstrated that the activation of PKC attenuates insulin signalling cascade and make N2a cells insulin-resistant.

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Acknowledgements

We gratefully acknowledge the Indian Institute of Technology-Delhi, New Delhi, India for its support.

Funding

DM is a recipient of Senior Research Fellowship from CSIR, Government of India. C.S.D was supported by a grant from the Department of Science and Technology (DST), Government of India, New Delhi, India (SR/S2/JCB-24/2008(G), dated 30 December 2008).

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  1. Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi, 110016, India

    Devanshi Mishra & Chinmoy Sankar Dey

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  1. Devanshi Mishra
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  2. Chinmoy Sankar Dey
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C.S.D. conceived the idea; D.M did all the experiments; CSD and DM wrote the manuscript and approved the final version of the manuscript.

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Correspondence to Chinmoy Sankar Dey.

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Mishra, D., Dey, C.S. Protein Kinase C Attenuates Insulin Signalling Cascade in Insulin-Sensitive and Insulin-Resistant Neuro-2a Cells. J Mol Neurosci 69, 470–477 (2019). https://doi.org/10.1007/s12031-019-01377-x

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