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Impaired neutrophil store-mediated calcium entry in Type 2 diabetes

Lookup NU author(s): Dr Andrew Advani, Emerita Professor Sally Marshall, Dr Trevor Thomas

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Abstract

Background: In Type 2 diabetes impaired neutrophil function leads to increased bacterial infection and cardiovascular disease. Many neutrophil functions depend on calcium signalling, which involves release of calcium from intracellular stores and subsequently translocation of stores via the cytoskeleton to the plasma membrane, causing store-mediated calcium entry (SMCE) into the cell. We hypothesized that in Type 2 diabetes there would be a defect in SMCE. Materials and methods: Neutrophils were prepared from patients with Type 2 diabetes (DM, n = 15) and controls (NC, n = 15). Free cytosolic calcium [Ca2+]i was measured with Fura-2 in resting cells and after stimulation of calcium release with fMLP and thapsigargin. Results: Baseline [Ca2+]i was higher in neutrophils from the patients than the controls (NC 65 ± 5 nM, DM 80 ± 4 nM, P < 0.05). However, after fMLP-treatment [Ca2+]i was significantly lower in the patients (NC 301 ± 28 nM, DM 210 ± 20 nM, P < 0.01).The greater increase in controls was not observed when cells were treated with fMLP in the absence of extracellular calcium (- fold increase NC 2.9 ± 0.5, DM 2.7 ± = 0.3). Treatment of cells with thapsigargin caused a similar greater increase in [Ca2+]i in the controls than in the patients that was not seen in the absence of extracellular calcium (- fold increase with Ca2+ NC 5.2 ± 1.0, DM 3.0 ± 0.4, P < 0.05; fold increase without Ca2+ NC 2.5 ± 0.4, DM 2.2 ± 0.2). Conclusions: In Type 2 diabetes there is a defect in neutrophil calcium signalling which results in a lesser increase in free cytosolic calcium owing to impaired influx across the plasma membrane. Abnormal calcium signalling is likely to be important in the pathogenesis of diabetic complications.


Publication metadata

Author(s): Advani A, Marshall SM, Thomas TH

Publication type: Article

Publication status: Published

Journal: European Journal of Clinical Investigation

Year: 2004

Volume: 34

Issue: 1

Pages: 43-49

ISSN (print): 0014-2972

ISSN (electronic): 1365-2362

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1365-2362.2004.01291.x

DOI: 10.1111/j.1365-2362.2004.01291.x

PubMed id: 14984437


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