Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA.
Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL, USA; Center for Neuroscience Initiative, Auburn University, Auburn, AL, USA.
Biochem Biophys Res Commun. 2019 Jul 5;514(4):1285-1289. doi: 10.1016/j.bbrc.2019.04.162. Epub 2019 May 18.
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.
先前我们实验室的工作表明，TrkA 在胰岛素信号通路中扮演了一个新的角色。TrkA 的激酶活性对于其与胰岛素受体（IR）和胰岛素受体底物-1（IRS-1）的相互作用以及在 PC12 细胞中激活 Akt 和 Erk5 是至关重要的。在这里，我们在链脲佐菌素（STZ）诱导的 1 型糖尿病大鼠的大脑中表明，无活性的 proNGF 的表达升高，而成熟的 NGF 的表达减少。此外，与对照组相比，STZ 诱导的糖尿病大鼠中 TrkA 的酪氨酸磷酸化减少。共免疫沉淀实验的结果表明，TrkA 与 IR 和 IRS-1 的相互作用在糖尿病大鼠的大脑中也减少了。此外，与对照组相比，STZ 糖尿病大鼠中 IR 和 IRS-1 的酪氨酸磷酸化以及 Akt 的激活减少。我们的结果表明，NGF-TrkA 受体参与胰岛素信号传递，并在 STZ 诱导的糖尿病大鼠的大脑中受损。
