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.
Miyagawa
S
S
Department of Paediatrics, Hiroshima University School of Medicine, Japan.
Kobayashi
M
M
Konishi
N
N
Sato
T
T
Ueda
K
K
D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000276:immunology / Q000378:metabolism; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology
D000906:Antibodies; D016895:Culture Media, Serum-Free; D007328:Insulin; D019089:Stem Cell Factor; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin