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

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2019 Jul 22

PMID 31327153

Citations 4

Authors

Devanshi Mishra

Chinmoy Sankar Dey

Affiliations

Soon will be listed here.

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.

Citing Articles

PKCα Isoform Inhibits Insulin Signaling and Aggravates Neuronal Insulin Resistance.

Mishra D, Reddy I, Dey C Mol Neurobiol. 2023; 60(11):6642-6659.

PMID: 37470970 DOI: 10.1007/s12035-023-03486-6.

PP1γ regulates neuronal insulin signaling and aggravates insulin resistance leading to AD-like phenotypes.

Yadav Y, Sharma M, Dey C Cell Commun Signal. 2023; 21(1):82.

PMID: 37085815 PMC: 10120118. DOI: 10.1186/s12964-023-01071-x.

PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.

Sharma M, Dey C Cell Commun Signal. 2022; 20(1):179.

PMID: 36376971 PMC: 9664818. DOI: 10.1186/s12964-022-00987-0.

Role of Akt isoforms in neuronal insulin signaling and resistance.

Sharma M, Dey C Cell Mol Life Sci. 2021; 78(23):7873-7898.

PMID: 34724097 PMC: 11073101. DOI: 10.1007/s00018-021-03993-6.

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