Grote C W, Morris J K, Ryals J M, Geiger P C, Wright D E
Department of Anatomy and Cell Biology, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Exp Diabetes Res. 2011;2011:212571. doi: 10.1155/2011/212571. Epub 2011 Jun 15.
Insulin signaling depends on tyrosine phosphorylation of insulin receptor substrates (IRSs) to mediate downstream effects; however, elevated serine phosphorylation of IRS impairs insulin signaling. Here, we investigated IRS protein expression patterns in dorsal root ganglia (DRG) of mice and whether their signaling was affected by diabetes. Both IRS1 and IRS2 are expressed in DRG; however, IRS2 appears to be the prevalent isoform and is expressed by many DRG neuronal subtypes. Phosphorylation of Ser(731)IRS2 was significantly elevated in DRG neurons from type 1 and type 2 diabetic mice. Additionally, Akt activation and neurite outgrowth in response to insulin were significantly decreased in DRG cultures from diabetic ob/ob mice. These results suggest that DRG neurons express IRS proteins that are altered by diabetes similar to other peripheral tissues, and insulin signaling downstream of the insulin receptor may be impaired in sensory neurons and contribute to the pathogenesis of diabetic neuropathy.
胰岛素信号传导依赖于胰岛素受体底物（IRSs）的酪氨酸磷酸化来介导下游效应；然而，IRS丝氨酸磷酸化水平升高会损害胰岛素信号传导。在此，我们研究了小鼠背根神经节（DRG）中IRS蛋白的表达模式以及它们的信号传导是否受糖尿病影响。IRS1和IRS2均在DRG中表达；然而，IRS2似乎是主要的异构体，并且由许多DRG神经元亚型表达。1型和2型糖尿病小鼠DRG神经元中Ser（731）IRS2的磷酸化显著升高。此外，来自糖尿病ob/ob小鼠的DRG培养物中，胰岛素刺激下的Akt激活和神经突生长显著降低。这些结果表明，DRG神经元表达的IRS蛋白与其他外周组织一样会因糖尿病而改变，胰岛素受体下游的胰岛素信号传导在感觉神经元中可能受损，并导致糖尿病神经病变的发病机制。
