Pharmacologic PPAR-γ Activation Reprograms Bone Marrow Macrophages and Partially Rescues HSPC Mobilization in Human and Murine Diabetes.

Mobilization of hematopoietic stem/progenitor cells (HSPC) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce in stromal cells and retain HSPC. BM adipocytes are another source of CXCL12 that blunts mobilization.

Diabetes mellitus impairs circulating proangiogenic granulocytes.

Aims/hypothesis: Cardiovascular risk in diabetes is at least in part attributable to defective angiogenesis. Since diabetes negatively affects blood cells involved in angiogenesis, we herein evaluated whether diabetes impairs proangiogenic granulocytes (PAGs).

Methods: We characterised and quantified PAGs as CD49d granulocytes in peripheral blood of participants with type 2 or type 1 diabetes and in non-diabetic control participants.

The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo.

Aims: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis.

Methods: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months.

NETosis Delays Diabetic Wound Healing in Mice and Humans.

Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue.