TRPM5-/- 小鼠胰岛高频葡萄糖诱导的 Ca2+ 振荡缺失与葡萄糖耐量受损相关。
Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice.
机构信息
Laboratory of Ion Channel Research and Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, B-3001 Louvain, Belgium.
出版信息
Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5208-13. doi: 10.1073/pnas.0913107107. Epub 2010 Mar 1.
Abstract
Glucose homeostasis is critically dependent on insulin release from pancreatic beta-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V(m)) and the cytosolic calcium level (Ca(2+)). We propose that TRPM5, a Ca(2+)-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca(2+)-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5(-/-) cells. Ca(2+)-imaging and electrophysiological analysis show that glucose-induced oscillations of V(m) and Ca(2+) have on average a reduced frequency in Trpm5(-/-) islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5(-/-) pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5(-/-) mice.
摘要
葡萄糖内稳态的维持依赖于胰岛β细胞分泌的胰岛素，而胰岛素的释放又严格受到膜电位（V(m)）和胞浆钙离子浓度(Ca(2+))葡萄糖浓度依赖性波动的调控。我们提出，瞬时受体电位阳离子通道亚家族 M 成员 5（TRPM5）是葡萄糖诱导胰岛素分泌的正向调节因子。免疫荧光显示 TRPM5 在胰岛中有表达。在 Trpm5(-/-)细胞中，一种具有 TRPM5 样特性的 Ca(2+)-激活非选择性阳离子电流显著减少。钙成像和电生理分析显示，葡萄糖诱导的 V(m)和Ca(2+)波动的频率在 Trpm5(-/-)胰岛中平均降低，这主要是由于快波动的缺失。因此，从 Trpm5(-/-)胰岛中葡萄糖诱导的胰岛素释放显著减少，导致 Trpm5(-/-)小鼠的葡萄糖耐量受损。
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