The relationship between GPR40 and lipotoxicity of the pancreatic β-cells as well as the effect of pioglitazone

► GPR40 mediates the short-term effects of FFAs on GSIS through the role of PDX-1 and GLUT2. ► GPR40 does not mediate the chronic toxic effects of FFAs on β-cell function. ► The reverse role of pioglitazone on lipotoxicity of β-cells may be related with GPR40.