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

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.