期刊
DIABETES
卷 51, 期 11, 页码 3245-3253出版社
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.51.11.3245
关键词
-
资金
- NHLBI NIH HHS [HL61974] Funding Source: Medline
Two sarcoendoplasmic reticulum Ca2+-ATPases, SERCA3 and SERCA2b, are expressed in pancreatic islets. Immunocytochemistry showed that SERCA3 is restricted to beta-cells in the mouse pancreas. Control and SERCA3-deficient mice were used to evaluate the role of SERCA3 in beta-cell cytosolic-free Ca2+ concentration ([Ca2+](c)) regulation, insulin secretion, and glucose homeostasis. Basal [Ca2+](c) was not increased by SERCA3 ablation. Stimulation with glucose induced a transient drop in basal [Ca2+](c) that was suppressed by inhibition of all SERCAs with thapsigargin (TG) but unaffected by selective SERCA3 ablation. Ca2+ mobilization by acetylcholine was normal in SERCA3-deficient beta-cells. In contrast, [Ca2+](c), oscillations resulting from intermittent glucose-stimulated Ca2+ influx and [Ca2+](c) transients induced by pulses of high K+ were similarly affected by SERCA3 ablation or TG pretreatment of control islets; their amplitude was increased and their slow descending phase suppressed. This suggests that, during the decay of each oscillation, the endoplasmic reticulum releases Ca2+ that was pumped by SERCA3 during the upstroke phase. SERCA3 ablation increased the insulin response of islets to 15 mmol/l glucose. However, basal and postprandial plasma glucose and insulin concentrations in SERCA3-deficient mice were normal. In conclusion, SERCA2b, but not SERCA3, is involved in basal [Ca2+](c) regulation in beta-cells. SERCA3 becomes operative when [Ca2+], rises and is required for normal [Ca2+](c) oscillations in response to glucose. However, a. lack of SERCA3 is insufficient in itself to alter glucose homeostasis or impair insulin secretion in mice.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据