GH PREINCUBATION FAILS TO INDUCE RESISTANCE TO THE MITOGCNIC ACTION OF INSULIN IN A PYGMY T-CELL LINE

In T-cell lines lioin normal individuals transformed by the HTLV-II retrovirus, we have shown that (1) GH preincubation completely inhibits the normal insulin-induced two-peak clonal response, and (2) direct clonal stimulation of GH on T-cells is mediated via local IGF-1. In the current study, we sought determine (I) if the ability of GH preincubation to induce resistance to the mitogenic action of insulin is also mediated by IGF-1 and (2) if a Pyymy T-cell line (previously shown to be both GH- and IGF-1-resistant in direct stimulation assays) would or would not become insulin-resistant following either GH or IGF-1 preincubation. T-cell lines from 3 normals and I Pygmy were studied. Colony formation was assessed in response to insulin (a) alone (1.2-13.2 × 10³ pmol/L), following 2 hr preincubalion with either (b) GH (50 μg/L) or (c) IGF-1 (8 μg/L), and (d) following 1 hr preincubation willi αIR3, a monoclonal antibidy against the IGf-1 receptor, and then 2 hr with GH. The following mean (±SE) refuses (first peak/second peak) were noted (*p<0.001 vs insulin alone):

These daia indicate that, in normal T-cell lines, either (b) GH or (c) IGF-1 preincubation induces resistance to insulin-induced clonogenesis. Since, in normals, GH-induced insulin resistance can be blocked by preincubation with αIR3 (d), this action of GH must be mediated through a local IGF-1 loop. Therefore, in the Pygmy T-cell line, since there was no significant reduction in insulin responsiveness following either GH or IGF-1 preincubation, the data suggest that the ygmy is IGF-1-resistant and support our earlier findings of resistance to the direct stimulatory effects of GH and IGF-1.