Circulating Neutrophil Extracellular Trap Levels in Well-Controlled Type 2 Diabetes and Pathway Involved in Their Formation Induced by High-Dose Glucose

• Miyoshi, Arina

• Yamada, Mai

• Shida, Haruki

• Nakazawa, Daigo

• Kusunoki, Yoshihiro

• Nakamura, Akinobu

• Miyoshi, Hideaki

• Tomaru, Utano

• Atsumi, Tatsuya

• Ishizu, Akihiro

Abstract

Objectives: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. Methods: Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. Results: Serum MPO-DNA complex levels were significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. Conclusions: Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose.

Journal

• Pathobiology

  Pathobiology 83 (5), 243-251, 2016

  Karger

Keywords

• Aldose reductase inhibitor
• Microvascular complications
• Myeloperoxidase-DNA complex
• Neutrophil extracellular trap
• Polyol pathway
• Type 2 diabetes

Details

• CRID: 1050282813997197824
• NII Article ID: 120005906798
• NII Book ID: AA1077272X
• ISSN: 14230291
• ISSN: 10152008
• HANDLE: 2115/61981
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles