2. Academic Validation
  3. 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) ameliorated dexamethasone induced hepatic gluconeogenesis through activation of Akt/FoxO1 pathway

  • Biochem Biophys Res Commun. 2017 Nov 4;493(1):286-290. doi: 10.1016/j.bbrc.2017.09.029.
Yanan Shi 1,  Jiayun Qiao 2,  Biao Mu 1,  Bingfeng Zuo 3,  Jihong Yuan 4
Affiliations

Affiliations

  • 1 Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, 300070 Tianjin, China.
  • 2 Tianjin Institute of Animal Husbandry and Veterinary Medicine, Tianjin Xiqing District Jin Jing Highway 17 Kilometers, 300381 Tianjin, China.
  • 3 Department of Cell Biology and Research Centre of Basic Medical Science, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, 300070 Tianjin, China.
  • 4 Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, No.22 Qixiangtai Road, Heping District, 300070 Tianjin, China. Electronic address: jyuan@tmu.edu.cn.
PMID: 28911865 DOI: 10.1016/j.bbrc.2017.09.029
Abstract

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.

Keywords

Akt; Hepatic gluconeogenesis; K145; SphK2.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z