Nerve growth factor receptor TrkA signaling in streptozotocin-induced type 1 diabetes rat brain.

Previous work from our lab demonstrated a new role of TrkA in the insulin signaling pathway. The kinase activity of TrkA is essential for its interaction with the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) and activation of Akt and Erk5 in PC12 cells. Here we show in brain from streptozotocin (STZ)-induced type 1 diabetic rats that the expression of the inactive proNGF is elevated, whereas the expression of mature NGF is reduced. In addition, tyrosine phosphorylation of TrkA is decreased in STZ-induced diabetes compared to control. Results of the co-immunoprecipitation experiments indicate that the interaction of TrkA with the IR and IRS-1 is also reduced in the brain of diabetic rats. Moreover, tyrosine phosphorylation of the IR and IRS-1, and Akt activation is decreased in STZ diabetes compared to control. Our results suggest that the NGF-TrkA receptor is involved in insulin signaling and is impaired in the brain of STZ-induced diabetic rats.