Li Chenchen, Zhu Jing, Wei Siying, Ye Xiaoyi, Yang Lanzexin, Wang Zinan, Chen Yan
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
J Nutr Biochem. 2023 Apr;114:109275. doi: 10.1016/j.jnutbio.2023.109275. Epub 2023 Jan 18.
Diabetes is caused by the interplay between genetic and environmental factors, therefore changes of lifestyle and dietary patterns are the most common practices for diabetes intervention. Protein restriction and caloric restriction have been shown to improve diabetic hyperglycemia in both animal models and humans. We report here the effectiveness of intermittent protein restriction (IPR) for the intervention of diabetes in Zucker diabetic fatty (ZDF) rats. Administration of IPR significantly reduced hyperglycemia and decreased glucose production in the liver. IPR protected pancreatic islets from diabetes-mediated damages as well as elevated the number and the proliferation activity of β cells. Single-cell RNA sequencing performed with isolated islets from the ZDF rats revealed that IPR was able to reverse the diabetes-associated β cell dedifferentiation. In addition, diabetic β cells in ZDF rats were associated with increased expressions of islet amyloid polypeptide, chromogranin and genes involved in endoplasmic reticulum stress. A β cell dedifferentiation marker Cd81 was also increased in the β cells of diabetic rats. In contrast, the expressions of D-box binding PAR bZIP transcription factor Dbp and immediate-early response genes were reduced in the diabetic β cells. In conclusion, these results indicated that IPR is effective in glycemic control and β cell protection in a diabetic rat model. In addition, diabetes in ZDF rats is associated with changes in the expression of genes involved in many facets of β cell functions.
糖尿病由遗传和环境因素相互作用引起，因此改变生活方式和饮食模式是糖尿病干预最常见的做法。蛋白质限制和热量限制已被证明在动物模型和人类中均可改善糖尿病高血糖。我们在此报告间歇性蛋白质限制（IPR）对Zucker糖尿病肥胖（ZDF）大鼠糖尿病干预的有效性。实施IPR可显著降低高血糖并减少肝脏中的葡萄糖生成。IPR保护胰岛免受糖尿病介导的损伤，并增加β细胞数量和增殖活性。对ZDF大鼠分离的胰岛进行的单细胞RNA测序显示，IPR能够逆转与糖尿病相关的β细胞去分化。此外，ZDF大鼠的糖尿病β细胞与胰岛淀粉样多肽、嗜铬粒蛋白以及内质网应激相关基因的表达增加有关。糖尿病大鼠的β细胞中β细胞去分化标志物Cd81也增加。相反，糖尿病β细胞中D盒结合PAR bZIP转录因子Dbp和即刻早期反应基因的表达降低。总之，这些结果表明IPR在糖尿病大鼠模型中对血糖控制和β细胞保护有效。此外，ZDF大鼠的糖尿病与β细胞功能多个方面相关基因表达的变化有关。
