Intracellular Hyaluronan Synthesis Impairs Hematopoiesis in Diabetes that can be Prevented by Heparin

Abstract

Hyperglycemia in diabetes induces impairment of hematopoiesis, an important consequence in bone marrow (BM) that contributes to chronic complications in advanced diabetes. The alterations to blood cells associated with diabetes mellitus (DM) pathologies have been carefully and extensively documented, but the underlying mechanism(s) is still unclear. Our recent publication indicates that aberrant intracellular synthesis of hyaluronan (HA) by hyperglycemic dividing BM progenitors is the central mechanism involved. This study demonstrated that macrophages that divided from progenitor cells in hyperglycemia are pro-inflammatory (Mpi) and that the presence of low concentrations of heparin (~20 nM) prevented the intracellular HA synthesis and promoted a tissue repair (Mtr) phenotype. Here, we briefly describe how our new studies of abnormal intracellular hyaluronan synthesis impairs hematopoiesis in diabetes and its regulation by heparin.