THE 3-PHOSPHORYLATED PHOSPHOINOSITIDE RESPONSE OF 3T3-L1 PREADIPOSE CELLS EXPOSED TO INSULIN, INSULIN-LIKE GROWTH-FACTOR-I, OR PLATELET-DERIVED GROWTH-FACTOR

We compared the pattern of 3-phosphorylated phosphoinositides produced by confluent 3T3-L1 preadipose cells upon exposure to growth factors that either induce differentiation (insulin, insulin-like growth facto r-1) or do not (platelet-derived growth factor). Following addition of insulin or insulin-like growth factor-1, PI(3,4,5)P-3 rapidly rose, o n average, to levels tenfold over basal. PI(3,4)P-2 either did not cha nge (after insulin) or slightly increased (1.5 fold). Time course stud ies with insulin demonstrated that the rise in PI(3,4,5)P-3 peaked by 1 minute, and levels then remained steady over 30 minutes. Dose-respon se experiments showed that insulin at a concentration of 1 nM was suff icient for the PI(3,4,5)P-3 response. Insulin failed to increase PI(3, 4)P-2 at any of the time points or at any of the doses used. In contra st, after addition of platelet-derived growth factor, both PI(3,4)P-2 and PI(3,4,5)P-3 rose concurrently and to comparable extents. These da ta suggest that one possible mechanism contributing to insulin/insulin -like growth factor-1-induced 3T3-L1 preadipose cell differentiation i s a distinct pattern of 3-phosphorylated phosphoinositide accumulation , defined by a prominent increase in PI(3,4,5)P-3 with no (in the case of insulin), or a minimal (in the case of IGF-1), rise in PI(3,4)P-2.