The pathogenesis of diabetic peripheral neuropathy (DPN) is complex and not well understood. Recently, oxidative stress and endoplasmic reticulum (ER) stress induced by hyperglycemia have been demonstrated to play a critical role in neuronal apoptosis, which then contributing to DPN. However, the specific molecular mechanism that underlies the hyperglycemia-induced neuronal stresses and apoptosis remains largely unknown. In this study, we demonstrated for the first time that Pim1 kinase is a positive modulator of dorsal root ganglion (DRG) neuron survival in vitro. Hyperglycemia causes compensatory upregulation of Pim1 kinase in the DRG neurons, which provides protection against high glucose-induced oxidative stress and ER stress. Pharmacological inhibition of Pim1 not only sensitizes the stress response to high glucose in the DRG neurons, but also accelerates the apoptosis of DRG neurons in vitro. Therefore, our work provides experimental evidence for the prevention of high glucose-induced neuronal stress and apoptosis by targeting Pim1 kinase.

糖尿病周围神经病变 (DPN) 的发病机制很复杂，尚不清楚。最近，高血糖诱导的氧化应激和内质网 (ER) 应激已被证明在神经元凋亡中起关键作用，进而导致 DPN。然而，高血糖引起的神经元应激和细胞凋亡的具体分子机制在很大程度上仍然未知。在这项研究中，我们首次证明 Pim1 激酶是体外背根神经节 (DRG) 神经元存活的正调节剂。高血糖导致 DRG 神经元中 Pim1 激酶的补偿性上调，这提供了针对高葡萄糖诱导的氧化应激和 ER 应激的保护。Pim1 的药理学抑制不仅使 DRG 神经元对高糖的应激反应敏感，但也加速了体外DRG神经元的凋亡。因此，我们的工作为通过靶向 Pim1 激酶预防高糖诱导的神经元应激和细胞凋亡提供了实验证据。