Sphingolipid regulators of cellular dysfunction in Type 2 diabetes mellitus: a systems overview

Abstract Climbing obesity rates have contributed to worldwide increases in obesity-associated diseases, including the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Sphingolipids, an important class of structural and signaling lipids, have emerged as key players in the development and pathogenesis of insulin resistance and T2DM. More specifically, sphingolipids have been demonstrated to play integral roles in lipotoxicity and other aspects of pathogenesis in T2DM, although the cellular mechanisms by which this occurs and by which sphingolipid metabolism is dysregulated in T2DM remain under investigation. This review summarizes current knowledge of sphingolipid metabolism and signaling in key organs and tissues affected by T2DM, including the pancreas, adipose tissue, skeletal muscle, cardiovascular system and liver, and highlights areas that ripe for future investigation.