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

Abstract

Summary. 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 1 /Kit 1 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 1 /Kit 1 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 CD341 /Kit 1 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.

SDF-1 Genotype Influences Insulin-Dependent Mobilization of Adult Progenitor Cells in Type 2 Diabetes

“…It is beyond the scope of this pilot study to elucidate the molecular mechanisms by which insulin interacts with PC mobilization. However, influences of insulin on chemotaxis and inflammatory reactions (16 -18), as well as proliferation of PCs (19), should be considered, and ongoing studies should aim to answer some of the questions addressed. This pilot study is not sufficient to rule out minor effects of hyperglycemia and oxidative stress on PC mobilization and demands for larger clinical trials to study the effects of different insulin preparations (insulin analogs) on PC mobilization and development of diabetes complications.…”

Comparison of Glycated Albumin (GA) and Glycated Hemoglobin (HbA1c) in Type 2 Diabetic Patients: Usefulness of GA for Evaluation of Short-term Changes in Glycemic Control

“…These reports raise the possibility that insulin deficiency may increase GA formation through the down-regulation of albumin synthesis and prolongation of the half-life of this protein, while insulin resistance and compensatory hyperinsulinemia may decrease GA formation through the upregulation of albumin metabolism. Regarding the RBC lifespan, insulin may also influence erythropoiesis [11], while an increase of Hb and the RBC count has been observed in subjects with the insulin resistance syndrome [12] or metabolic syndrome [13]. Although these reports suggest that GA and HbA1c may be affected by plasma insulin level and insulin resistance through influences on albumin metabolism or erythropoiesis, direct information about whether these factors actually modify the formation of GA or HbA1c in diabetic patients has not been obtained.…”

NACA is a positive regulator of human erythroid-cell differentiation

“…However, understanding the mechanisms that direct myeloid-cell development and differentiation might require further events linking external stimuli and geneexpression cascades. As an example, in the erythroid-cell lineage (a subclass of the myeloid lineages), in addition to the well-established role of both the erythropoietin/erythropoietinreceptor (Epo/Epo-R) pair and the GATA1 transcription factor, other extrinsic signaling molecules including Wnt/frizzled (Van Den Berg et al, 1998), TGFβ (Zermati et al, 2000), fibroblast growth factors (Huber et al, 1998), growth-factorindependence 1B (Osawa et al, 2002), insulin and insulin-like growth factor (Miyagawa et al, 2000), and intrinsically acting factors such as caspases (Zermati et al, 2001) have been reported to be important for erythropoiesis. Further identification of either novel molecules or complex sets of interactions between already-identified crucial transcription factors and co-factors might help to elucidate the molecular mechanisms that control the myeloid differentiation process.…”