Role of p21ras in insulin-stimulated glucose transport in 3T3-L1 adipocytes.

The proto-oncogene p21ras has been implicated as an essential intermediate in several actions of the hormone insulin. This study examines the role of p21ras in the signaling pathways by which insulin increases hexose transport in differentiated 3T3-L1 adipose cells, a model system for study of the metabolic effects of the hormone on a physiological target tissue. Introduction of constitutively activated p21ras(G12V) by microinjection into 3T3-L1 adipocytes stimulated the expression of the ubiquitous glucose transporter, GLUT1, in the absence of insulin. Moreover, introduction of dominant inhibitory forms of p21ras or neutralizing antibodies directed against p21ras blocked the insulin-induced increase in GLUT1 expression. In contrast, microinjection of activating or inhibitory forms of p21ras had no effect on translocation of the "insulin-responsive" glucose transporter, GLUT4, to the cell surface. These results indicate that p21ras mediates the insulin-induced increase in GLUT1 expression in 3T3-L1 adipocytes but is not involved in the translocation of GLUT4 that leads to acute increases in glucose transport.