Background:Neither glucose nor FFA alone cause clinically meaningful pancreatic β-cell toxicity, especially in subjects with normal or glucose intolerance.The down-and up-regulations of autophagy under the conditions of glucotoxicity and lipotocicity, respectively, are active in β-cells.We hypothesized that glucotoxicity-induced autophagic (lipophagic) insufficiency causes the cytotoxic lipid accumulation resulting in glucolipotoxicty in β-cells.