Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, China.
Department of Pediatrics, Pediatric Research Institute, University of Louisville School of Medicine, Louisville, Kentucky.
J Cell Mol Med. 2019 Aug;23(8):5794-5807. doi: 10.1111/jcmm.14504. Epub 2019 Jun 20.
To detect the changes in the liver function in both male and female OVE26 mice from young to adults for better understanding of type 1 diabetes-induced hepatic changes, OVE26 mice and wild-type FVB mice were raised in the same environment without any intervention, and then killed at 4, 12, 24 and 36 weeks for examining liver's general properties, including pathogenic and molecular changes. The influence of diabetes on the bodyweight of male and female mice was different. Both male and female OVE26 mice did not obtain serious liver injury or non-alcoholic fatty liver disease, manifested by mild elevation of plasma alanine transaminase, and less liver lipid content along with significantly suppressed lipid synthesis. Uncontrolled diabetes also did not cause hepatic glycogen accumulation in OVE26 mice after 4 weeks. Oxidative stress test showed no change in lipid peroxidation, but increased protein oxidation. Changed endoplasmic reticulum stress and apoptosis along with increased antioxidant capacity was observed in OVE26 mice. In conclusion, uncontrolled type 1 diabetes did not cause hepatic lipid deposition most likely because of reduced lipids synthesis in response to insulin deficiency. Enhanced antioxidant capacity might not only prevent the occurrence of severe acute liver injury but also the self-renewal, leading to liver dysfunction.
为了更好地了解 1 型糖尿病引起的肝变化,我们检测了雄性和雌性 OVE26 小鼠从幼年到成年的肝功能变化。我们将 OVE26 小鼠和野生型 FVB 小鼠在相同的环境中饲养,不进行任何干预,然后在 4、12、24 和 36 周时处死,以检查肝脏的一般特性,包括病理和分子变化。糖尿病对雄性和雌性小鼠体重的影响不同。雄性和雌性 OVE26 小鼠均未出现严重肝损伤或非酒精性脂肪肝,表现为血浆丙氨酸转氨酶轻度升高,肝脂质含量减少,脂质合成明显受抑制。4 周后,未控制的糖尿病也未导致 OVE26 小鼠肝糖原积累。氧化应激试验显示脂质过氧化无变化,但蛋白质氧化增加。在 OVE26 小鼠中观察到内质网应激和凋亡改变,同时抗氧化能力增强。总之,未控制的 1 型糖尿病可能不会导致肝脂质沉积,这很可能是由于胰岛素缺乏导致脂质合成减少。增强的抗氧化能力不仅可以预防严重的急性肝损伤,还可以促进肝脏的自我更新,导致肝功能障碍。