کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2165939 1549318 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets
ترجمه فارسی عنوان
اختلالات ناشی از استرس ناشی از سیگنالینگ کلسیم داخل سلولی و ترشح انسولین در جزایر پانکراس
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی


• 48-h exposure to different stressors impaired peak glucose-stimulated Ca2+ equally.
• Thapsigargin and cytokines (ER stressors) affect Ca2+; minimal insulin release effect.
• FFAs, 28G, and rotenone (metabolic stressors) affected Ca2+-dependent insulin release.
• Conclusion: mild metabolic stress impacts insulin release more than mild ER stress.

In healthy pancreatic islets, glucose-stimulated changes in intracellular calcium ([Ca2+]i) provide a reasonable reflection of the patterns and relative amounts of insulin secretion. We report that [Ca2+]i in islets under stress, however, dissociates with insulin release in different ways for different stressors. Islets were exposed for 48 h to a variety of stressors: cytokines (low-grade inflammation), 28 mM glucose (28G, glucotoxicity), free fatty acids (FFAs, lipotoxicity), thapsigargin (ER stress), or rotenone (mitochondrial stress). We then measured [Ca2+]i and insulin release in parallel studies. Islets exposed to all stressors except rotenone displayed significantly elevated [Ca2+]i in low glucose, however, increased insulin secretion was only observed for 28G due to increased nifedipine-sensitive calcium-channel flux. Following 3–11 mM glucose stimulation, all stressors substantially reduced the peak glucose-stimulated [Ca2+]i response (first phase). Thapsigargin and cytokines also substantially impacted aspects of calcium influx and ER calcium handling. Stressors did not significantly impact insulin secretion in 11 mM glucose for any stressor, although FFAs showed a borderline reduction, which contributed to a significant decrease in the stimulation index (11:3 mM glucose) observed for FFAs and also for 28G. We also clamped [Ca2+]i using 30 mM KCl + 250 μM diazoxide to test the amplifying pathway. Only rotenone-treated islets showed a robust increase in 3–11 mM glucose-stimulated insulin secretion under clamped conditions, suggesting that low-level mitochondrial stress might activate the metabolic amplifying pathway. We conclude that different stressors dissociate [Ca2+]i from insulin secretion differently: ER stressors (thapsigargin, cytokines) primarily affect [Ca2+]i but not conventional insulin secretion and ‘metabolic’ stressors (FFAs, 28G, rotenone) impacted insulin secretion.

Chronic treatment with physiological doses of various stressors has similar net effects on intracellular calcium following glucose stimulation but strikingly different effects on pathways leading to insulin release in pancreatic islets.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 57, Issues 5–6, May 2015, Pages 366–375
نویسندگان
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