Role of Diacylglycerol Kinases in Glucose and Energy Homeostasis

Diacylglycerol kinases (DGKs) catalyze a reaction that converts diacylglycerol (DAG) to phosphatidic acid (PA). DAG and PA act as intermediates of de novo lipid synthesis, cellular membrane constituents, and signaling molecules. DGK isoforms regulate a variety of intracellular processes by terminating DAG signaling and activating PA-mediated pathways. The ten DGK isoforms are unique, not only structurally, but also in tissue-specific expression profiles, subcellular localization, regulatory mechanisms, and DAG preferences, suggesting isoform-specific functions. DAG accumulation has been associated with insulin resistance; however, this concept is challenged by opposing roles of DGK isoforms in the development of type 2 diabetes and obesity despite elevated DAG levels. This review focuses on the tissue- and isoform-specific role of DGK in glucose and energy homeostasis.