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Diabetologia
Published in: Diabetologia 4/2007

01-04-2007 | Article

Sphingosine kinase 1 participates in insulin signalling and regulates glucose metabolism and homeostasis in KK/Ay diabetic mice

Authors: M. M. Ma, J. L. Chen, G. G. Wang, H. Wang, Y. Lu, J. F. Li, J. Yi, Y. J. Yuan, Q. W. Zhang, J. Mi, L. Sh. Wang, H. F. Duan, C. T. Wu

Published in: Diabetologia | Issue 4/2007

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Abstract

Aims/hypothesis

The aim of this study was to determine the potential role of sphingosine kinase 1 (SPHK1), a key sphingolipid metabolic enzyme, in glucose metabolism and homeostasis.

Methods

SMMC-7721 hepatoma cells and C2C12 myotube cells were used to explore the role of SPHK1 in glucose uptake in vitro. KK/Ay type 2 diabetic mice, which were transfected with adenovirus harbouring the human SPHK1 gene by i.v. injection, were used to investigate the glucose-lowering effects of SPHK1 in vivo.

Results

The basal glucose uptake and the insulin-stimulated glucose uptake in both 7721 cells and C2C12 cells were markedly enhanced when SPHK1 was overexpressed by adenovirus-mediated gene transfer, whereas they were substantially reduced when the expression of SPHK1 was inhibited or the activity of SPHK1 was blocked. Insulin could activate SPHK1 of both cell lines in a dose-dependent manner. SPHK1 gene delivery significantly reduced the blood glucose level of KK/Ay diabetic mice, but had no effect on that of normal animals. It also attenuated elevated levels of plasma insulin, NEFA, triacylglycerol, cholesterol and LDL, significantly ameliorated hyperglycaemia-induced injury of liver, heart and kidney, and enhanced phosphorylation of insulin-signalling kinases such as Akt and glycogen synthase kinase 3β in livers of the diabetic animals.

Conclusions/interpretation

SPHK1 is involved in insulin signalling and plays an important role in the regulation of glucose and fat metabolism; adenovirus-mediated SPHK1 gene transfer might provide a novel strategy in the treatment of type 2 diabetes mellitus.
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Metadata
Title
Sphingosine kinase 1 participates in insulin signalling and regulates glucose metabolism and homeostasis in KK/Ay diabetic mice
Authors
M. M. Ma
J. L. Chen
G. G. Wang
H. Wang
Y. Lu
J. F. Li
J. Yi
Y. J. Yuan
Q. W. Zhang
J. Mi
L. Sh. Wang
H. F. Duan
C. T. Wu
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 4/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0589-5

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