کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7638825 | 1494807 | 2018 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prolonged stimulation of insulin release from MIN6 cells causes zinc depletion and loss of β-cell markers
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کلمات کلیدی
L-type voltage-gated calcium channelsGSISMREZnTZIPL-VGCCZIP transportersTrpqPCRCa2+ - Ca2 +Quantitative PCR - PCR کمیZn2+ - ZN 2+β-Cells - β-سلول هاGene expression - بیان ژنGlucose-stimulated insulin secretion - ترشح انسولین تحریک شده توسط گلوکزDedifferentiation - تشخیص دادنInductively-coupled plasma mass spectrometry - طیف سنجی جرم پلاسما به صورت القاییICP-MS - طیفسنجی جرمی پلاسمای جفتشده القاییMetal response element - عنصر پاسخ فلزیTranscription factors - عوامل رونویسیZinc - فلز رویMetallothionein - متالوتونیئینMODY - مدtransient receptor potential - پتانسیل گیرنده گذراKATP channels - کانال های KATPATP-sensitive potassium channels - کانال های پتاسیم حساس به ATPCalcium ions - یون کلسیمZinc ions - یونهای روی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Zinc is integral for the normal function of pancreatic β-cells in glycaemic control. Large amounts of zinc are secreted from β-cells following insulin exocytosis and regulated replenishment is required, which is thought to be mediated by the ZIP family of zinc importer proteins. Within Type 2 Diabetic patients, β-cells are stressed through prolonged stimulation by hyperglycaemia and this is thought to be a major factor contributing to loss of β-cell identity and mass. However, the consequences for the β-cell zinc status remain largely unexplored. We used inductively coupled plasma mass spectrometry (ICP-MS) to show that 24â¯h treatment of MIN6 cells with potassium chloride, mimicking hyperglycaemic stimulation, reduces the total cellular zinc content 2.8-fold, and qPCR to show an increase in mRNA expression for metallothioneins (Mt1 and Mt2) following 4 and 24â¯h of stimulation, suggestive of an early rise in cytosolic zinc. To determine which ZIP paralogues may be responsible for zinc replenishment, we used immunocytochemistry, Western blot and qPCR to demonstrate initial ZIP1 protein upregulation proceeded by downregulation of mRNA coding for ZIP1, ZIP6, ZIP7 and ZIP14. To assign a biological significance to the decreased total cellular zinc content, we assessed expression of key β-cell markers to show downregulation of mRNA for MafA, Mnx-1, Nkx2.2 and Pax6. Our data suggest hyperglycaemia-induced zinc depletion may contribute to loss of β-cell markers and promote β-cell dedifferentiation through disrupting expression of key transcription factors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Trace Elements in Medicine and Biology - Volume 49, September 2018, Pages 51-59
Journal: Journal of Trace Elements in Medicine and Biology - Volume 49, September 2018, Pages 51-59
نویسندگان
Rebecca Lawson, Wolfgang Maret, Christer Hogstrand,