کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2166278 1549323 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling
چکیده انگلیسی

In obesity and the early stages of type 2 diabetes (T2D), proinflammatory cytokines are mildly elevated in the systemic circulation. This low-grade systemic inflammation exposes pancreatic islets to these circulating cytokines at much lower levels than seen within the islet during insulitis. These low-dose effects have not been well described. We examined mouse islets treated overnight with a low-dose cytokine combination commonly associated with inflammation (TNF-alpha, IL-1 beta, and IFN-gamma). We then examined islet function primarily using intracellular calcium ([Ca2+]i), a key component of insulin secretion and cytokine signaling. Cytokine-treated islets demonstrated several features that suggested dysfunction including excess [Ca2+]i in low physiological glucose (3 mM), reduced responses to glucose stimulation, and disrupted [Ca2+]i oscillations. Interestingly, islets taken from young db/db mice showed similar disruptions in [Ca2+]i dynamics as cytokine-treated islets. Additional studies of control islets showed that the cytokine-induced elevation in basal [Ca2+]i was due to both greater calcium influx through L-type-calcium-channels and reduced endoplasmic reticulum (ER) calcium storage. Many of these cytokine-induced disruptions could be reproduced by SERCA blockade. Our data suggest that chronic low-grade inflammation produces circulating cytokine levels that are sufficient to induce beta-cell dysfunction and may play a contributing role in beta-cell failure in early T2D.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 48, Issues 2–3, August–September 2010, Pages 133–142
نویسندگان
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