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

• Published in: Journal of molecular neuroscience Vol. 69; no. 3; pp. 470 - 477
• Main Authors: Mishra, Devanshi, Dey, Chinmoy Sankar
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2019; Springer Nature B.V
• Subjects: Acetic acid; AKT protein; Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Brain; Cell activation; Cell Biology; Cell Line, Tumor; Cognitive ability; Enzyme Activation - drug effects; Glucose; Glucose - metabolism; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Insulin; Insulin - pharmacology; Insulin resistance; Insulin Resistance - physiology; Kinases; Long-term potentiation; Mice; Nerve Tissue Proteins - physiology; Neuroblastoma; Neurochemistry; Neurology; Neurons - drug effects; Neurons - metabolism; Neurosciences; Phorbol 12-myristate 13-acetate; Protein kinase C; Protein Kinase C - physiology; Proteins; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Signal Transduction - drug effects; Signaling; Substrates; Synaptic plasticity; Tetradecanoylphorbol Acetate - pharmacology; PKC; Insulin resistance; Glucose uptake; Neuron; Insulin signalling
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-019-01377-x

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.