Insulin and IGF-I stimulate normal and virally transformed T-lymphocyte cell growth in vitro

We used normal and HTLV-II-transformed T-lymphocytes as target cells to study clonal proliferative responses to physiologic and supraphysiologic concentrations of insulin and IGF-I. Responses of both growth factors were measured in the presence and absence of alpha IR-3, and IGF-I receptor-blocking antibody. A biphasic response to insulin was noted in all cell lines with the first peak [78 +/- 6.6% (mean +/- SE) above control] occurring at 1.4 or 1.6 nmol/liter and a second peak (84 +/- 4.9% above control) occurring at 18.0 nmol/liter. Following preincubation with alpha IR-3, the overall clonal profile in response to insulin was significantly reduced [F(7,56) = (10.4, p < .0001] as a result of blunting at high physiologic and supraphysiologic insulin concentrations, i.e., > or = 1.6 nmol/liter. As expected, the overall clonal profile in response to IGF-I was blocked by alpha IR-3 [F(4,32) = 11.6, p < .0001]. These data show that insulin at both physiologic and supraphysiologic concentrations, as well as IGF-I, stimulate virally transformed T-lymphoblast growth. The significant inhibition of growth responses to high concentrations of insulin and to IGF-I by alpha IR-3 suggests mediation of these effects through the IGF-I receptor. Similar studies were performed using freshly isolated, phytohemagglutinin (PHA)-stimulated T-lymphocytes. The overall response to insulin was significantly reduced compared to the profile of transformed T-lymphoblasts [F(7,70) = 4.9, p = .0002] as a result of blunting at physiologic insulin concentrations < 1.8 nmol/liter. In response to IGF-I, the clonal profile of PHA-stimulated T-lymphocytes was slightly reduced compared to that of virally transformed T-lymphoblasts [F(4,40) = 3.4, p = .0174]. Thus, both insulin and IGF-I receptor-effector mechanisms are involved in the growth of virally transformed T-lymphoblasts, whereas the IGF-I receptor-effector mechanism appears to play a more significant role in the growth of normal, mitogen-activated T-lymphocytes.