INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) STIMULATE GLUT4 GLUCOSE-TRANSPORTER TRANSLOCATION IN XENOPUS OOCYTES

1. The heterologous expression of glucose transporters GLUT4 and GLUT1 in Xenopus oocytes has been shown to cause a differential targeting o f these glucose-carrier isoforms to cellular membranes and a distinct induction of glucose transport activity. In this study we have evaluat ed the effect of insulin and insulinlike growth factor I (IGF-I) on gl ucose uptake and glucose transporter distribution in Xenopus oocytes e xpressing mammalian GLUT4 and GLUT1 glucose carriers. 2. Insulin and I GF-1 stimulated 2-deoxyglucose uptake in GLUT4-expressing oocytes, but not in GLUT1-expressing oocytes or in water-injected oocytes. The sti mulatory effect of insulin and IGF-I on 2-deoxyglucose uptake in GLUT4 -expressing oocytes occurred via activation of the IGF-I receptor. 3. Subcellular-fractionation studies indicated that insulin and IGF-I sti mulated translocation of GLUT4 to the cell surface of the oocyte. 4. I ncubation of intact oocytes with insulin stimulated phosphatidylinosit ol 3-kinase activity, an effect that was blocked by the additional pre sence of wortmannin. Furthermore, wortmannin totally abolished the ins ulin-induced stimulation of 2-deoxyglucose uptake in GLUT4-expressing oocytes. 5. In this study, both the insulin-induced GLUT4 carrier tran slocation and GLUT4-dependent insulin-stimulated glucose transport hav e been reconstituted in the Xenopus oocyte. These observations, togeth er with the fact that wortmannin, as found in adipocytes, inhibits ins ulin-stimulated glucose transport in oocytes, suggest that the heterol ogous expression of GLUT4 in oocytes is a useful experimental model by which to study the cell biology of insulin-induced GLUT4 translocatio n.