Stimulatory effect of human insulin on erythroid progenitors (cfu‐e and bfu‐e) in human cd34⁺separated bone marrow cells and the relationship between insulin and erythropoietin

Abstract

Abstract. Erythropoietin is known to be effective for the treatment of anemia in chronic renal failure, but the efficacy of erythropoietin for anemia in other diseases is not so great. Insulin exerts a growth promoting activity in various kinds of cells. In the present study, the effects of insulin on erythroid progenitors (colony forming units-erythroid, CFU-E; and burst forming units-erythroid, BFU-E) in human bone marrow were examined at various concentrations of recombinant human erythropoietin (rh-Epo) to clarify the relationship between erythropoietin and insulin. Human insulin stimulated the formation of CFU-E and BFU-E in the presence of three concentrations (0.25, 5, and 100 Ulml) of rh-Epo. Stimulatory effects of human insulin on CFU-E and BFU-E were also observed in the nonphagocytic and nonadherent bone marrow fraction (NP-NA fraction) and in the NP-NA and T cell-depleted fraction at each concentration of rh-Epo. Human insulin further stimulated the CFU-E and BFU-E growth in CD34' separated bone marrow cells. These results indicate that the enhancing effect of human insulin on erythroid progenitors is not mediated through monocytes and macrophages or T cells, suggesting a direct action on erythroid progenitors.

New aspects of the insulin resistance syndrome: impact on haematological parameters

“…This hypothesis seems supported by in vitro results showing that human insulin has a stimulatory effect on erythroid progenitors independently of plasma erythropoietin concentrations [8]. Of note, the effect on haematological parameters will have to be weighed against the hypoglycaemic effect of insulin.…”

“…The mechanism of the stimulatory effects of human insulin on human bone marrow CFU-E and BFU-E (burst forming unitserythroid) and the relation between insulin and erythropoietin have been previously investigated [8±9,20]. Briefly, the insulin receptor itself is thought to be involved in RBC proliferation and the insulin receptor (INS-R) has been detected on human erythropoietic cells at different stages of development, suggesting that human insulin acts at all stages of erythropoiesis [8]. Using a serum free system, it has been shown [20] that insulin needs to bind with its own receptor before stimulating the erythroid progenitors, suggesting a direct action of this hormone on CFU-E and BFU-E.…”

“…Furthermore, in multivariate analysis IR was significantly associated with red blood cell count independently of age, sex, WHR, plasma iron, drug intake and smoking habits. Not surprisingly, this model explained only 18 % of variance because ± even though CFU-E requires insulin for erythroid development [18] ± insulin activity is synergistic with, but not alternative to, the effect of erythropoietin on growth of erithroid progenitors [8,20,29]. Indeed, although insulin should be considered a co-factor of erythropoietin, it had no effect on erythropoiesis in the absence of erythropoietin [8,20].…”

The role of insulin (INS) and insulin-like growth factor-I (IGF-I) in regulating human erythropoiesis. Studies in vitro under serum-free conditions – comparison to other cytokines and growth factors

“…We also studied the development of BFU-E colonies compared to the effect of other cytokines and growth factors which have been reported to enhance erythropoiesis. 4,6,[16][17][18][19] Finally, we analyzed by FACS and RT-PCR the expression of INS-R and IGF-IR in the early progenitor cells and their more differentiated, cultured derivatives. Our results suggest that neither INS nor IGF-I are critical for human erythropoiesis.…”

Haematologic Response in Hyperglycaemic Rats Experimentally Induced with Alloxan

“…The medullary dsyerythropoeisis is attributable to lack of insulin in the peripheral and bone marrow circulation which is a vital co-factor for blast and progenitor cells of the erythroid series for proliferation and maturation [25,26]. Skudelski however proposes that destruction of the pancreatic beta cells of the experimental animal following alloxan induction results in sudden outburst of insulin and transient hypoglycaemic effect [2].…”