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Sphingosine 1-phosphate increases glucose uptake through trans-activation of insulin receptor.
- Source :
-
Cellular & Molecular Life Sciences . Oct2009, Vol. 66 Issue 19, p3207-3218. 12p. 1 Diagram, 6 Graphs. - Publication Year :
- 2009
-
Abstract
- Sphingosine 1-phosphate (S1P) is a bioactive lipid that acts through a family of G-protein-coupled receptors. Herein, we report evidence of a novel redox-based cross-talk between S1P and insulin signaling pathways. In skeletal muscle cells S1P, through engagement of its S1P2 receptor, is found to produce a transient burst of reactive oxygen species through a calcium-dependent activation of the small GTPase Rac1. S1P-induced redox-signaling is sensed by protein tyrosine phosphatase-1B, the main negative regulator of insulin receptor phosphorylation, which undergoes oxidation and enzymatic inhibition. This redox-based inhibition of the phosphatase provokes a ligand-independent trans-phosphorylation of insulin receptor and a strong increase in glucose uptake. Our results propose a new role of S1P, recognizing the lipid as an insulin-mimetic cue and pointing at reactive oxygen species as critical regulators of the cross-talk between S1P and insulin pathways. Any possible implication of S1P-directed insulin signaling in diabetes and insulin resistance remains to be established. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SPHINGOSINE
*LIPIDS
*INSULIN
*REACTIVE oxygen species
*PROTEINS
*PHOSPHORYLATION
Subjects
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 66
- Issue :
- 19
- Database :
- Academic Search Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 44217649
- Full Text :
- https://doi.org/10.1007/s00018-009-0106-3