Sphingosine 1-phosphate increases glucose uptake through trans-activation of insulin receptor

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• 作者：Elena Rapizzi ; Maria Letizia Taddei ; Tania Fiaschi ; Chiara Donati ; Paola Bruni and Paola Chiarugi
• 关键词：Sphingosine 1 ; phosphate ; Insulin ; Insulin receptor ; Protein ; tyrosine phosphatase ; Reactive oxygen species ; Glucose uptake
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2009
• 出版时间：October, 2009
• 年：2009
• 卷：66
• 期：19
• 页码：3207-3218
• 全文大小：509.8 KB

文摘

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.