Figure 2.

Role of S1P metabolism on insulin in peripheral tissues in response to palmitate. In hepatocytes, palmitate increases intracellular S1P content through SphK1/2 activities. According to studies, produced S1P seems to exert a direct positive action on insulin signaling, or a negative action by stimulating its S1P2 receptors. In muscle cells, palmitate increased intracellular S1P through SphK1 activity, which favors Akt activation, glucose uptake, and glycogen synthesis in response to insulin. In adipocytes, palmitate increases intracellular S1P to inhibit Akt activation in response to insulin. Produced S1P also favors expression of pro-inflammatory cytokines that will contribute to inhibit Akt activity. CDase: ceramidase. GLUT4: glucose transporter 4. IRS: insulin receptor substrate. PI3K: phosphatidylinositol-3-kinase. SphK: sphingosine kinase. S1P2: S1P receptor 2.