INSULIN-RESPONSIVE HUMAN ADIPOCYTES EXPRESS 2 GLUCOSE-TRANSPORTER ISOFORMS AND TARGET THEM TO DIFFERENT VESICLES

We have characterized the insulin-dependent increase in glucose transp ort in human adipocytes using subcellular fractionation and antibodies specific for the two isoforms of the glucose transporter that are exp ressed in these cells. Plasma membranes isolated from untreated human fat cells contain the erythroid/GLUT1 isoform of the glucose transport er almost exclusively whereas the muscle-fat/GLUT4 transporter isoform is most abundant in intracellular microsomal membranes in resting cel ls. After exposure of adipocytes to insulin, the muscle-fat isoform is dramatically increased in the plasma membrane whereas the erythroid i soform barely changes in response to insulin. Thus, the total insulin- mediated increase in plasma membrane glucose transporters, confirmed b y affinity labeling of both transporter isoforms, must be due to the i ncrease in the muscle-fat/GLUT4 transporter. The two isoforms exist in different vesicle populations as shown by immunoadsorption of the mus cle fat isoform-containing vesicles which are essentially devoid of th e erythroid transporter. These data indicate that the insulin-mediated increases in glucose transport in human fat cells is a result of the translocation of vesicles uniquely containing the muscle-fat glucose t ransporter isoform.