Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Veterans Affairs Medical Center, Baltimore, MD 21201, USA.
Int J Mol Sci. 2022 Apr 28;23(9):4887. doi: 10.3390/ijms23094887.
Axon degeneration in diabetic peripheral neuropathy (DPN) is associated with impaired NAD metabolism. We tested whether the administration of NAD precursors, nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), prevents DPN in models of Type 1 and Type 2 diabetes. NMN was administered to streptozotocin (STZ)-induced diabetic rats and STZ-induced diabetic mice by intraperitoneal injection at 50 or 100 mg/kg on alternate days for 2 months. mice The were fed with a high fat diet (HFD) for 2 months with or without added NR at 150 or 300 mg/kg for 2 months. The administration of NMN to STZ-induced diabetic rats or mice or dietary addition of NR to HFD-fed mice improved sensory function, normalized sciatic and tail nerve conduction velocities, and prevented loss of intraepidermal nerve fibers in skin samples from the hind-paw. In adult dorsal root ganglion (DRG) neurons isolated from HFD-fed mice, there was a decrease in NAD levels and mitochondrial maximum reserve capacity. These impairments were normalized in isolated DRG neurons from NR-treated mice. The results indicate that the correction of NAD depletion in DRG may be sufficient to prevent DPN but does not significantly affect glucose tolerance, insulin levels, or insulin resistance.
在糖尿病周围神经病变 (DPN) 中，轴突退化与 NAD 代谢受损有关。我们测试了 NAD 前体烟酰胺单核苷酸 (NMN) 或烟酰胺核糖 (NR) 的给药是否可以预防 1 型和 2 型糖尿病模型中的 DPN。通过腹腔注射，NMN 以 50 或 100mg/kg 的剂量在 2 个月内每隔一天给链脲佐菌素 (STZ) 诱导的糖尿病大鼠和 STZ 诱导的糖尿病小鼠给药。将高脂肪饮食 (HFD) 喂养 2 个月，同时或不添加 NR（150 或 300mg/kg）喂养 2 个月。NMN 的给药可改善 STZ 诱导的糖尿病大鼠或小鼠的感觉功能，使坐骨神经和尾巴神经传导速度正常化，并防止后足皮肤样本中表皮内神经纤维的丢失。从 HFD 喂养的小鼠分离出的成年背根神经节 (DRG) 神经元中，NAD 水平和线粒体最大储备能力下降。在 NR 处理的小鼠分离的 DRG 神经元中，这些损伤得到了纠正。结果表明，DRG 中 NAD 耗竭的纠正可能足以预防 DPN，但对葡萄糖耐量、胰岛素水平或胰岛素抵抗没有显著影响。
