3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) ameliorated dexamethasone induced hepatic gluconeogenesis through activation of Akt/FoxO1 pathway

3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) is identified as a selective SphK2 inhibitor. It was previously reported as an anti-tumor agent, in this study we demonstrated that K145 was able to regulate hepatic gluconeogenesis and improve glucose intolerance i...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2017-11, Vol.493 (1), p.286-290
Main Authors: Shi, Yanan, Qiao, Jiayun, Mu, Biao, Zuo, Bingfeng, Yuan, Jihong
Format: Article
Language:English
Subjects:
Akt
Animals
Dexamethasone - administration & dosage
Forkhead Box Protein O1 - metabolism
Gluconeogenesis - drug effects
Gluconeogenesis - physiology
Glucose - metabolism
Hepatic gluconeogenesis
K145
Liver - drug effects
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-akt - metabolism
Signal Transduction - drug effects
Signal Transduction - physiology
SphK2
Thiazolidinediones - administration & dosage
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Summary:3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) is identified as a selective SphK2 inhibitor. It was previously reported as an anti-tumor agent, in this study we demonstrated that K145 was able to regulate hepatic gluconeogenesis and improve glucose intolerance in mice. C57BL/6 mice treated with dexamethasone injection were used as experimental animals, which exhibited impaired glucose tolerance and increased gluconeogenetic enzymes. After K145 treatment, we found that the impairment of glucose tolerance and gluconeogenetic genes mRNA expression were improved. Besides, both in vivo and in votro studies suggested that K145 stimulated insulin dependent Akt phosphorylation and subsequently activates FoxO1 phosphorylation therefore inhibited gluconeogenetic genes expression including PEPCK and G6pase. Our study figures out a potential extent increase the value of developing K145 as therapeutic candidate for diabetes. •An improvment of glucose tolerance and gluconeogentic enzyme exoression by K145 is raised.•The mechanism of K145 regulated gluconeogenetic genes expression is proposed.•An extended application for K145 is found.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.09.029