Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 514, Issue 4, Pages 1285-1289Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.04.162
Keywords
NGF; TrkA; Insulin receptor; Insulin signaling; Tyrosine phosphorylation
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Funding
- Alabama Agricultural Experiment Station
- Hatch/Multistate Funding Program
- AAES Award for Interdisciplinary Research (AAES-AIR)
- Cellular and Molecular Biosciences Graduate Research Fellowship
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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. (C) 2019 Elsevier Inc. All rights reserved.
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