Preferential Activation of Microsomal Diacylglycerol/Protein Kinase C Signaling during Glucose Treatment (De Novo Phospholipid Synthesis) of Rat Adipocytes

Glucose has been reported to increase the de novo synthesis of diacylglycerol (DAG) and translocate and activate protein ki-nase C (PKC) in rat adipocytes. Presently, we examined the major subcellular site of PKC translocation/activation in re-sponse to glucose-induced DAG. Glucose rapidly increased DAG content and PKC enzyme activity in microsomes, but not in plasma membranes or other membranes, during a 30-min treatment of rat adipocytes. This glucose-induced increase in microsomal DAG was attended by increases in immunoreactive PKC a,,B, and E. Glucose-induced activation ofDAG/PKC sig-naling in microsomes was not associated with a change in the translocation of Glut4 transporters from microsomes to the plasma membrane, a biological response that is known to be stimulated by agonists, e.g., phorbol esters, which increase DAG/PKC signaling in plasma membranes, as well as in mi-crosomes. In conclusion, an increase in de novo phospholipid synthesis, as occurs during glucose treatment of rat adipocytes, primarily activates DAG/PKC signaling in microsomes; more-over, this signaling response and biological consequences thereof may differ from those of agonists that primarily stimu-late DAG/PKC signaling in the plasma membrane. (J. Clin