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Lookup NU author(s): Dr Andrew Advani,
Emerita Professor Sally Marshall,
Dr Trevor Thomas
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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.
Author(s): Advani A, Marshall SM, Thomas TH
Publication type: Article
Publication status: Published
Journal: European Journal of Clinical Investigation
ISSN (print): 0014-2972
ISSN (electronic): 1365-2362
PubMed id: 14984437
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