REQUIREMENT FOR PHOSPHOINOSITIDE 3-KINASE IN INSULIN-STIMULATED GLUT4TRANSLOCATION IN 3T3-L1 ADIPOCYTES

Insulin stimulates glucose transport in muscle and fat cells by induci ng the redistribution of a specific glucose transporter, GLUT4 from in tracellular vesicles to the cell surface. Phosphoinositide (PI) 3-kina se has been implicated as a key intermediate in insulin-stimulated glu cose transport by studies that have examined the effects of wortmannin and LY294002, which are thought to be specific inhibitors of this enz yme. However, the specificity of these compounds for PI 3-kinase has r ecently been questioned. Epidermal growth factor, which activates mito gen-activated protein kinase in mouse 3T3-L1 adipocytes, has now been shown to have no effect on PI 3-kinase activity or GLUT4 translocation in these cells. Furthermore, microinjection of a dominant negative mu tant of the 85-kDa subunit of PI 3-kinase, which lacks a binding site for the catalytic 110-kDa subunit, inhibited GLUT4 translocation induc ed by insulin in 3T3-L1 adipocytes; microinjection of the wild-type pr otein had no effect. These observations indicate that PI 3-kinase is n ecessary for insulin-induced GLUT4 translocation and glucose transport in adipocytes. (C) 1995 Academic Press, Inc.