期刊
PATHOBIOLOGY
卷 83, 期 5, 页码 243-251出版社
KARGER
DOI: 10.1159/000444881
关键词
Aldose reductase inhibitor; Microvascular complications; Myeloperoxidase-DNA complex; Neutrophil extracellular trap; Polyol pathway; Type 2 diabetes
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [15K15105]
- Grants-in-Aid for Scientific Research [15K15105] Funding Source: KAKEN
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. (C) 2016 The Author(s) Published by S. Karger AG, Basel
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