The Role of PPAR-delta in the adaptation of β-cells to high glucose levels

Introduction: Pancreatic β-cells are programmed to adapt to elevated levels of glucose by increasing their insulin secretory function. The molecular mechanisms of this process are not fully understood. Peroxisome proliferator-activated receptor-delta (PPAR-delta), which has been shown to play essential roles in regulation of lipid and carbohydrate metabolism, has also been found to function as a lipid sensor in β-cells. Recently, we have found that high glucose levels activate PPAR-delta in vascular cells. Current reports have indicated that 4-hydroxyalkenals (the products of peroxidation of poly-unsaturated fatty acids), such as 4-hydroxynonenal (4-HNE), serve as endogenous ligands of PPAR-delta. Therefore, we asked whether the adaptation of β-cells to hyperglycemia is mediated by PPAR-delta and what could be the endogenous ligand of this nuclear receptor.