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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)364-376
Number of pages13
JournalJournal of Genetics and Genomics
Volume49
Issue number4
DOIs
StatePublished - Apr 2022
Externally publishedYes

Keywords

  • AKT
  • De novo lipogenesis
  • Functionalized gadofullerene
  • Glycolipid metabolism
  • Type 2 diabetes

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