学術雑誌論文 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

83 ( 5 )  , pp.243 - 251 , 2016 , Karger
ISSN:1015-20081423-0291
NII書誌ID(NCID):AA1077272X
内容記述
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.
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http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/61981/1/Pathobiology_Miyoshi%20et%20al.pdf

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