A recent study has identified protein tyrosine phosphatase receptor type J (PTPRJ) as a negative regulator of insulin signaling in neuronal cells.

The research highlights the role of the PTP enzyme family in insulin signaling, suggesting that aberrant PTPs could serve as therapeutic targets for type 2 diabetes.

Notably, the study confirmed a direct interaction between PTPRJ and the insulin receptor (INSR), with PTPRJ recruitment increasing upon insulin stimulation.

In murine models, PTPRJ was found to inhibit insulin signaling, with PTPRJ-deficient mice demonstrating improved insulin sensitivity and glucose tolerance.

PTPRJ deficiency was linked to increased cellular stress markers, which in turn affected cell differentiation and neurite outgrowth.

RNA sequencing of PTPRJ-deficient cells revealed upregulated gene clusters associated with glucose uptake and lipid synthesis.

Additionally, the study found differential expression of 16 calcium ion transporters in Ptprj knockout cells, indicating PTPRJ's involvement in neurotransmission.

Corresponding author Kai Kappert, MD, from Charité University Medicine Berlin, emphasized that insulin resistance is prevalent in both peripheral organs and the brain.

Previous research has linked insulin resistance to neurodegenerative diseases such as Alzheimer's and Parkinson's, suggesting a broader impact on cognitive health.

The findings imply that central insulin resistance may connect type 2 diabetes, obesity, and cognitive impairments.

Published in the Journal of Neuroendocrinology, the study suggests potential implications for gene therapy in treating insulin resistance-related diseases.

The authors conclude that PTPRJ is crucial for regulating insulin signaling and neuronal development, opening avenues for future research and therapeutic applications.