Functionalized gadofullerene ameliorates impaired glycolipid metabolism in type 2 diabetic mice  

作　　者：Jin Wu Yingbo Chen Xue Li Liyuan Ran Xiangdong Liu Xiaoshuang Wang Mingming Zhen Shanshan Shao Li Zeng Chunru Wang Bin Liang Jiajun Zhao Yingjie Wu 

机构地区：[1]Shandong Provincial Hospital,Shandong Laboratory Animal Center,Science and Technology Innovation Center,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,Shandong 250021,China [2]Institute for Genome Engineered Animal Models of Human Diseases,Dalian Medical University,Dalian,Liaoning 116044,China [3]Beijing National Laboratory for Molecular Sciences,Key Laboratory of Molecular Nanostructure and Nanotechnology,CAS Research/Education Center for Excellence in Molecular Sciences,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China [4]Center for Life Sciences,School of Life Sciences,Yunnan University,Kunming,Yunnan 650091,China [5]Department of Molecular Pathobiology,New York University College of Dentistry,New York 10010,USA

出　　处：《Journal of Genetics and Genomics》2022年第4期364-376,共13页遗传学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (31871163, 81471000);the Ministry of Science and Technology of China (2014DFA32120)

摘　　要：The soaring global prevalence of diabetes makes it urgent to explore new drugs with high efficacy and safety.Nanomaterial-derived bioactive agents are emerging as one of the most promising candidates for biomedical application.In the present study,we investigated the anti-diabetic effects of a functionalized gadofullerene(GF)using obese db/db and non-obese mouse model of type 2 diabete mellitus(MKR)mouse type 2 diabetes mellitus(T2DM)models.In both mouse models,the diabetic phenotypes,including hyperglycemia,impaired glucose tolerance,and insulin sensitivity,were ameliorated after two or four weeks of intraperitoneal administration of GF.GF lowered blood glucose levels in a dose-dependent manner.Importantly,the restored blood glucose levels could persist ten days after withdrawal of GF treatment.The hepatic AKT/GSK3β/FoxO1 pathway is shown to be the main target of GF for rebalancing gluconeogenesis and glycogen synthesis in vivo and in vitro.Furthermore,GF treatment significantly reduced weight gain of db/db mice with reduced hepatic fat storage by the inhibition of de novo lipogenesis through m TOR/S6K/SREBP1 pathway.Our data provide compelling evidence to support the promising application of GF for the treatment of T2DM.

关 键 词：Functionalized gadofullerene Type 2 diabetes Glycolipid metabolism AKT De novo lipogenesis 

分 类 号：R587.1[医药卫生—内分泌]