Kim Tae Woo, Oum Sae-Jong, Lim Ji Hee, Kim Yaeni, Kim Eun Nim, Jin Yongjie, Hong Yu Ah, Chae Seung Yun, Choi Bum Soon, Kim Hye Won, Park Cheol Whee
Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Cell Commun Signal. 2025 Jul 16;23(1):342. doi: 10.1186/s12964-025-02326-5.
Disruption of energy support to peripheral nerves leads to dysfunction and degeneration of both neuronal axons and Schwann cells (SCs).
We evaluated the effects of the adiponectin receptor (AdipoR) agonist, AdipoRon on diabetic peripheral neuropathy (DPN) using mice, murine ND7/23 cells, and human SCs.
AdipoRon improved sensorimotor function and restored nerve phenotypes in the sciatic nerve and paw skin of mice by reducing systemic oxidative stress and insulin resistance. AdipoRon restored impaired oxidative stress response, apoptosis, and autophagy activity through increased AdipoR1/R2-intracellular Ca-CaMKKβ expression as well as LKB1/AMPK-PPARα/PGC-1α/Nrf2 phosphorylation. It also decreased mTOR phosphorylation, which is related to the preservation of mitochondria in axons and SCs, and improved MCT1/2/4 expression and lactate and ATP/AMP levels in the sciatic nerve of mice. In ND7/23 cells and SCs, AdipoRon decreased oxidative stress and apoptosis while increasing autophagy by suppressing high glucose- and palmitate-induced cellular and mitochondrial oxidative stress, activating the same signaling as in the sciatic nerve. These protective changes were induced by providing energy substrate, lactate and ATP, through the increased expression of MCT1/2/4, facilitating metabolic communication between neurons and SCs.
AdipoRon may play an important role in preventing DPN by ameliorating oxidative stress, apoptosis, and autophagy, strengthening metabolic support for neurons and SCs under diabetic conditions.
外周神经能量支持的中断会导致神经元轴突和施万细胞（SCs）功能障碍和退化。
我们使用小鼠、鼠源ND7/23细胞和人SCs评估脂联素受体（AdipoR）激动剂AdipoRon对糖尿病性周围神经病变（DPN）的影响。
AdipoRon通过降低全身氧化应激和胰岛素抵抗，改善了小鼠坐骨神经和爪皮肤的感觉运动功能并恢复了神经表型。AdipoRon通过增加AdipoR1/R2-细胞内Ca-CaMKKβ表达以及LKB1/AMPK-PPARα/PGC-1α/Nrf2磷酸化，恢复了受损的氧化应激反应、细胞凋亡和自噬活性。它还降低了与轴突和SCs中线粒体保存相关的mTOR磷酸化，并改善了小鼠坐骨神经中MCT1/2/4的表达以及乳酸和ATP/AMP水平。在ND7/23细胞和SCs中，AdipoRon通过抑制高糖和棕榈酸诱导的细胞和线粒体氧化应激，激活与坐骨神经相同的信号传导，从而降低氧化应激和细胞凋亡，同时增加自噬。这些保护性变化是通过增加MCT1/2/4的表达提供能量底物乳酸和ATP来诱导的，促进了神经元和SCs之间的代谢通讯。
AdipoRon可能通过改善氧化应激、细胞凋亡和自噬，在糖尿病条件下加强对神经元和SCs的代谢支持，从而在预防DPN中发挥重要作用。
