Mechanisms of lipotoxicity-induced dysfunction and death of human pancreatic beta cells under obesity and type 2 diabetes conditions.

The term "pancreatic beta-cell lipotoxicity" refers to the detrimental effects of free fatty acids (FFAs) on a wide variety of cellular functions. Basic research in the field has primarily analyzed the effects of palmitic acid and oleic acid. The focus on these two physiological FFAs, however, ignores differences in chain length and degree of saturation. In order to gain a comprehensive understanding of the lipotoxic mechanisms, a wide range of structurally related FFAs should be investigated. Structure-activity relationship analyses of FFAs in the human EndoC-βH1 beta-cell line have provided a deep insight into the mechanisms of beta-cell lipotoxicity. This review focuses on the effects of a wide range of FFAs with crucial structural determinants for the development of lipotoxicity in human beta cells and documents an association between increased triglyceride stores in obesity and in type 2 diabetes.