Insulin and Insulin-Like Growth Factor I Support the Proliferation of Erythroid Progenitor Cells in Bone Marrow Through the Sharing of Receptors

Br J Haematol. 2000 Jun;109(3):555-62. doi: 10.1046/j.1365-2141.2000.02047.x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Dose-Response Relationship, Drug
  • Erythroid Precursor Cells / drug effects*
  • Erythroid Precursor Cells / metabolism
  • Erythropoietin / pharmacology
  • Humans
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Receptor, IGF Type 1 / immunology
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Insulin / immunology
  • Receptor, Insulin / metabolism
  • Stem Cell Factor / pharmacology

Substances

  • Antibodies
  • Culture Media, Serum-Free
  • Insulin
  • Stem Cell Factor
  • Erythropoietin
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Receptor, Insulin