Endothelin-1 reduces plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) and disrupts cortical actin structure in cultured adipocytes, leading to impaired translocation of the glucose transporter GLUT4 in response to both insulin and hyperosmotic stress.

Endothelin-1 binds to a receptor on the fat cell membrane, which triggers a local change that depletes a specific lipid called PIP2 and breaks down the mesh of filaments just under the membrane. Without this lipid and structural support, glucose transporters cannot move to the membrane to let sugar into the cell, even when insulin or high salt signals try to trigger the movement.