Sphingosine 1-phosphate increases glucose uptake through trans-activation of insulin receptor |
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Authors: | Elena Rapizzi Maria Letizia Taddei Tania Fiaschi Chiara Donati Paola Bruni Paola Chiarugi |
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Institution: | (1) Department of Biochemical Sciences, University of Florence, Viale G.B. Morgagni 50, 50134 Florence, Italy;(2) Interuniversity Institute of Myology, Florence, Italy; |
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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. |
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