Functionalized gadofullerene ameliorates impaired glycolipid metabolism in type 2 diabetic mice

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

doi:10.1016/j.jgg.2021.09.004

Volume 49 Issue 4

Apr. 2022

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Article Navigation > Journal of Genetics and Genomics > 2022 > 49(4): 364-376

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Functionalized gadofullerene ameliorates impaired glycolipid metabolism in type 2 diabetic mice

doi: 10.1016/j.jgg.2021.09.004

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

Funds:

This work was supported by the National Natural Science Foundation of China (31871163, 81471000)

the Ministry of Science and Technology of China (2014DFA32120).

Received Date: 2021-06-17
Accepted Date: 2021-09-01
Rev Recd Date: 2021-09-01
Publish Date: 2022-04-30

Abstract

Abstract

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 mTOR/S6K/SREBP1 pathway. Our data provide compelling evidence to support the promising application of GF for the treatment of T2DM.
- Functionalized gadofullerene,
- Type 2 diabetes,
- Glycolipid metabolism,
- AKT,
- De novo lipogenesis

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References(51)

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