Functionalized Gadofullerene Ameliorates Impaired Glycolipid Metabolism in Type 2 Diabetic Mice.

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 MKR mouse T2DM models. In both mouse models, the diabetic phenotypes including hyperglycemia, impaired glucose tolerance and insulin sensitivity were ameliorated following 2 or 4 weeks of i.p. administration of GF. GF lowered blood glucose levels in a dose-dependent manner. Importantly, the restored blood glucose levels could persist 10 days after withdrawal of GF treatment. The hepatic AKT/GSK3β/FoxO1 pathway is shown to be the main target of GF for re-balancing gluconeogenesis and glycogen synthesis in vivo and in vitro. In addition, 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.