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 dia-betes 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 mTOR/S6K/SREBP1 pathway.Our data provide compelling evidence to support the promising application of GF for the treatment of T2DM.

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

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;Institute for Genome Engineered Animal Models of Human Diseases,Dalian Medical University,Dalian,Liaoning 116044,China;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;Center for Life Sciences,School of Life Sciences,Yunnan University,Kunming,Yunnan 650091,China;Department of Molecular Pathobiology,New York University College of Dentistry,New York 10010,USA

遗传学报

[1]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-.Functionalized gadofullerene ameliorates impaired glycolipid metabolism in type 2 diabetic mice)[J].遗传学报,2022(04):364-376

gadofullerene,Nanomaterial,diabete

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