A recent study from Charité University of Medicine in Berlin has uncovered that the protein tyrosine phosphatase receptor type J (PTPRJ) negatively regulates insulin signaling in neurons, potentially impacting diabetes treatment strategies.
Lead author Dr. Kai Kappert and his team highlighted that Type 2 diabetes (T2D) is often linked to insulin resistance not only in peripheral organs like the liver and muscles but also in the brain. This central insulin resistance could be a common factor in T2D, obesity, and cognitive decline.
Previous research has suggested connections between insulin resistance and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. However, the exact mechanisms behind these associations remain unclear.
The study focused on PTP enzymes, which modulate various signaling pathways related to metabolism. PTPRJ was identified as a key negative regulator of insulin signaling in mouse models. Mice lacking PTPRJ exhibited increased insulin sensitivity and improved glucose tolerance.
Using gene editing, the researchers created a PTPRJ knockout model in mouse neuroblastoma cells, finding enhanced insulin signaling in these cells. They demonstrated a direct interaction between PTPRJ and the insulin receptor (INSR), which increased upon insulin stimulation.
Gene expression analysis revealed that the absence of PTPRJ positively regulated genes related to glucose metabolism and lipid synthesis. Additionally, they discovered altered expression of calcium ion (Ca2+) transporters, suggesting PTPRJ's role in neurotransmission.
The findings indicate that PTPRJ deficiency may hinder cell differentiation and neurite growth, highlighting its potential significance in nervous system development and diabetes treatment.