Insulin and insulin-like growth factor I support the proliferation of erythroid progenitor cells in bone marrow through the sharing of receptors

The effects of insulin and insulin-like growth factor I (IGF-I) on the proliferation of erythroid progenitor cells in bone marrow were studied in serum-deprived culture. Primitive human bone marrow cells were purified by cell sorting on the basis of the expression of CD34 and the Kit receptor Insulin and IGF-I with erythropoietin (EPO) dose dependently supported the formation of erythroid colonies of CD34(+)/Kit(+) cells in bone marrow The direct effect of insulin and IGF-I on the stimulation of primitive erythroid progenitor cells was confirmed by single-cell proliferation studies in serum-deprived liquid suspension culture, The addition of insulin and/or IGF-I to stem cell factor (SCF) resulted in an additive increase in the number of erythroid colonies. The erythroid colonies formed by insulin and IGF-I with EPO were different in size from those formed by SCF with EPO, These findings imply that erythroid progenitor cells responding to insulin and IGF-I might be at a different developmental stage of erythropoiesis from those responding to SCF in CD34(+)/Kit(+) cells. Similarly insulin and IGF-I with EPO supported the proliferation of the mature erythroid progenitor cells in light-density bone marrow mononuclear cells (LDBMCs). The addition of the anti-receptor antibody to IGF-I receptor or insulin receptor partially suppressed erythroid colony formation supported with insulin or IGF-I in both CD34(+)/Kit(+) cells and LDBMCs. The simultaneous addition of both receptor antibodies completely abrogated the erythroid colony formation. These results suggest that insulin and IGF-I directly stimulate the proliferation of the late stage of primitive erythroid progenitor cells and mature erythroid progenitor cells through the sharing of receptors.