The insulin-like growth factor II/mannose 6-phosphate receptor utilizes the same membrane compartments as GLUT4 for insulin-dependent trafficking to and from the rat adipocyte cell surface.

The insulin-like growth factor II (IGF-II)/mannose 6-phosphate (Man-6-P) receptor recycles in adipose cells between the cell surface and an intracellular storage pool, and the rate of this trafficking is markedly enhanced by insulin. We show here that the IGF-II/Man-6-P receptor is a constituent of the GLUT4-containing compartment ("GLUT4 vesicles") where it represents gp230, a major recycling protein detected earlier by cell surface biotinylation (Kandror, K. V., and Pilch, P. F. (1994) J. Biol. Chem. 269, 138-142). The GLUT4 vesicles include 10-15% of the total and all of the acutely insulin-responsive recycling population of the IGF-II/Man-6-P receptor. The main part of the IGF-II/Man-6-P receptor population is excluded from the pathway of GLUT4 trafficking and either resides permanently in intracellular membranes or has a much slower rate of cycling to the cell surface. Thus, GLUT4 vesicles mediate the insulin-dependent delivery to the cell surface of the IGF-II/Man-6-P receptor as well as the other recyclable proteins with extracellular functional domains (GLUT4 and the aminopeptidase gp160).