Glucotoxicity in the pancreatic beta-cell is defined as nonphysiological and potentially irreversible cellular damage induced by chronic exposure to supraphysiologic glucose concentrations, which leads to defective insulin secretion and worsening glucose regulation. Preservation of beta-cells, through tight glycemic regulation, is an essential component of the treatment strategy for type 2 diabetes. It is well known that one of the main mechanisms of glucotoxicity is chronic oxidative stress. Though free fatty acids (FFA) stimulate insulin secretion, chronically elevated FFA impairs pancreatic beta cell function in vitro and in vivo, which leads to the induction of lipotoxicity. FFAs move into cells through a passive concentration-dependent diffusion, and it has been reported that there are active transport systems to enhance FFA uptake . Fatty acid translocase cluster determinant 36 (CD36), which is part of the FFA transporter system, has been identified in several tissues such as muscle, liver, and insulin-producing cells . Several studies have reported that induction of CD36 increases uptake of FFA in INS-1 cells and Caco-2/15 cells, suggesting the functional interplay between glucose and FFA in terms of insulin secretion and oxidative metabolism. However, we do not currently know the regulating mechanism and physiological role of CD36 on glucotoxicity in pancreatic beta-cells. Also, the downstream and upstream targets of CD36 related signaling have not been defined. We would like to determine whether hyperglycemia enhances the expression of CD36, and whether the accompanying CD36 related signaling can affect pancreatic beta-cell function, and if inhibition of CD36 reverses the deteriorated beta-cell function.