Targeting Ceramides and Adiponectin Receptors in the Islet of Langerhans for Treating Diabetes.

ABSTRACT

Ceramides belong to the sphingolipid family and represent the central hub of the sphingolipid network. In obesity, oversupply of saturated fatty acids including palmitate raises ceramide levels which can be detrimental to cells. Elevated ceramides can cause insulin resistance, endoplasmic reticulum stress, and mitochondrial dysfunction. Studies over the last few decades have highlighted the role played by ceramides in pancreatic islet ß-cell apoptosis, especially under glucolipotoxic and inflammatory conditions. This review focuses on ceramides and adiponectin receptor signaling, summarizing recent advancements in our understanding of their roles in islet ß-cells and the discovery of zinc-dependent lipid hydrolase (ceramidase) activity of adiponectin receptors. The therapeutic potential of targeting these events to prevent islet ß-cell loss for treating diabetes is discussed.