Stimulation of human early and late erythropoietic progenitor cells by insulin: evidence for different mechanisms.

Abstract

In order to investigate cellular mechanisms involved in insulin stimulation of erythropoiesis, we have studied the response of early (BFU-e) and late (CFU-e) erythroid progenitor cells in a serum-free agar culture system. In this assay system, CFU-e proliferation occurred in media containing low-density lipoproteins, bovine serum albumin, transferrin and recombinant erythropoietin (rEPO). Insulin in physiological concentrations as low as 10(-12)M, added directly to cultures, augmented CFU-e colony formation. This stimulatory effect was also seen when monocyte- and T lymphocyte-depleted cells from normal donors were cultured. In contrast, BFU-e was not stimulated by media devoid of insulin. Occurrence of BFU-e colonies required the presence of insulin in concentrations higher than 10(-8)M. This insulin effect was not dependent on the presence of monocytes and T lymphocytes. Delayed addition studies of rEPO to insulin containing cultures revealed a slight but significant survival rate of CFU-e. A similar survival rate was found for BFU-e. From this, we conclude that insulin stimulates CFU-e by an EPO-like activity. For BFU-e, however, the decline in the number of bursts caused by EPO deprivation implies that insulin does not act directly as a burst-promoting activity but that it probably induces the release of this activity from non-adherent and T lymphocyte-depleted bone marrow cells.