Intermittent protein restriction protects isletβcells and improves glucose homeostasis in diabetic mice  

间歇性蛋白限制在糖尿病小鼠中保护胰岛β细胞并改善血糖稳态

作　　者：Siying Wei Chenchen Li Xuemei Luo Lanzexin Yang Long Yu Qintao Wang Zhuo-Xian Meng Tao Wang Yan Chen 韦思颖;李晨晨;罗雪梅;杨兰泽鑫;余龙;王钦涛;孟卓贤;王滔;陈雁(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 200031,China;School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China;Huzhou R&D Center for Nutrition and Health,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Huzhou 313000,China;Department of Pathology and Pathophysiology,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province,First Affliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]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 200031,China [2]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China [3]Huzhou R&D Center for Nutrition and Health,Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences,Huzhou 313000,China [4]Department of Pathology and Pathophysiology,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province,First Affliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310058,China

出　　处：《Science Bulletin》2022年第7期733-747,共15页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (31630036);the Ministry of Science and Technology of China (2016YFA0500103);the Chinese Academy of Sciences (QYZDJ-SSW-SMC008)

摘　　要：Diabetes is caused by the interplay between genetics and environmental factors, tightly linked to lifestyle and dietary patterns. In this study, we explored the effectiveness of intermittent protein restriction(IPR)in diabetes control. IPR drastically reduced hyperglycemia in both streptozotocin-treated and leptin receptor-deficient db/db mouse models. IPR improved the number, proliferation, and function of β cells in pancreatic islets. IPR reduced glucose production in the liver and elevated insulin signaling in the skeletal muscle. IPR elevated serum level of FGF21, and deletion of the Fgf21 gene in the liver abrogated the hypoglycemic effect of IPR without affecting β cells. IPR caused less lipid accumulation and damage in the liver than that caused by continuous protein restriction in streptozotocin-treated mice. Single-cell RNA sequencing using mouse islets revealed that IPR reversed diabetes-associated β cell reduction and immune cell accumulation. As IPR is not based on calorie restriction and is highly effective in glycemic control and β cell protection, it has promising translational potential in the future.糖尿病由遗传和环境因素相互作用导致,与生活方式和饮食密切相关.该研究探讨了一种间歇性蛋白限制(IPR)饮食方式对糖尿病的干预所用.研究发现, IPR可以迅速缓解链脲佐菌素诱导的1型糖尿病小鼠以及瘦素受体缺陷导致的2型糖尿病小鼠的高血糖症.在胰岛中, IPR可以增加β细胞数量、促进β细胞增殖,并改善β细胞功能;在外周组织中,IPR可以减少肝脏的糖异生并提高骨骼肌的胰岛素敏感性. IPR增加血清FGF21的浓度,在肝脏敲除Fg f21基因可以抵消IPR的降血糖作用,但对胰岛β细胞没有影响.与持续性低蛋白饮食相比, IPR对于糖尿病小鼠的肝脏脂肪积累和损伤更轻.小鼠胰岛单细胞测序揭示IPR可以逆转糖尿病导致的胰岛β细胞减少以及免疫细胞浸润. IPR这一高效控制血糖并保护胰岛β细胞的饮食方法不是基于热量限制,故IPR在未来可能具有较大的应用转化潜力.

关 键 词：Nutritional intervention Diabetes intervention Protein restriction ISLETS scRNA-seq 

分 类 号：TS201.4[轻工技术与工程—食品科学]