Insulin inhibits the JNK mediated cell death via upregulation of AKT expression in Schwann cells grown in hyperglycemia

Abstract

BACKGROUND: Schwann cells (SCs) are the glial cells of the peripheral nervous system, which forms a thick insulating structure around the axons. Hyperglycemia is known physiologic conditions in both type I and type II diabetes which causes diabetic neuropathy. But the SC possesses insulin receptors even though glucose uptake is independent of insulin. Since the insulin level is highly altered in diabetes, it is of greater importance to evaluate their role in the Schwann cell survival and death.

METHODS: Schwann cells were isolated from neonatal pups and grown with and without insulin in hyperglycemic medium to mimic diabetic condition for 24 and 48 h. We studied the cell viability using 3 (4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and mitochondrial membrane potential (MMP) assay at different time interval on SCs. We also studied the protein and gene expression of Protein Kinase B (AKT) and Jun N-terminal kinase (JNK), which are greatly involved in cell survival and cell death respectively.

RESULTS: The result shows that, high glucose levels for 48 h decrease the SC viability. Hyperglycemic condition induces the SC death by increasing the JNK expression which in turn reduces the MMP of glial cells. However, insulin administration for SCs grown in high glucose condition can reduce the JNK expression by activating AKT signaling pathway.

CONCLUSION: These observations demonstrate that the proper insulin balance is required for Schwann cells survival in hyperglycemic condition. Therefore, altered insulin signaling can be one of the reasons for demyelination of peripheral neurons in diabetic neuropathy.

Keywords

insulin / schwann cells / apoptosis / JNK / AKT / diabetic peripheral neuropathy

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Acknowledgments

MSM was supported by Junior Research Fellowship by Department of Science and Technology (DST). We thank Rohit Kumar H. G. and Kiran Kumar H. N. for critical reading and support.

This work was supported by grant (SERB No: SB/SO/AS-119/2012) from Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India (New Delhi).

Compliance with ethics guidelines

Mallahalli S Manu, Kuruvanthe S Rachana and Gopal M. Advirao declares that they have no conflict of interest.

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