Diabetes and Transcription Factors Group, Garvan Institute of Medical Research, Sydney, Australia.
PLoS One. 2012;7(6):e39462. doi: 10.1371/journal.pone.0039462. Epub 2012 Jun 28.
Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.
Gem-deficient mice were generated and their metabolic phenotype characterised by in vivo testing of glucose tolerance, insulin tolerance and insulin secretion. Calcium flux was measured in isolated islets.
Gem-deficient mice were glucose intolerant and had impaired glucose stimulated insulin secretion. Furthermore, the islets of Gem-deficient mice exhibited decreased free calcium responses to glucose and the calcium oscillations seen upon glucose stimulation were smaller in amplitude and had a reduced frequency.
These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling.
β细胞中葡萄糖刺激的胰岛素分泌是一个严格调控的过程，需要钙流来触发含胰岛素囊泡的胞吐作用。β细胞中钙处理的调节仍不完全清楚。Gem 是 RGK（Rad/Gem/Kir）家族的一员，调节其他细胞类型中钙通道的处理，Gem 过表达抑制胰岛素分泌细胞 Min6 中的胰岛素释放。本研究的目的是探讨 Gem 在胰岛素分泌中的作用。我们假设 Gem 可能调节胰岛素分泌，从而影响体内葡萄糖耐量。
生成 Gem 缺陷小鼠，并通过体内葡萄糖耐量、胰岛素耐量和胰岛素分泌试验对其代谢表型进行特征分析。在分离的胰岛中测量钙流。
Gem 缺陷小鼠表现出葡萄糖不耐受和葡萄糖刺激胰岛素分泌受损。此外，Gem 缺陷小鼠的胰岛对葡萄糖的游离钙反应降低，葡萄糖刺激时的钙振荡幅度较小，频率降低。
这些结果表明，Gem 通过调节钙信号在正常β细胞功能中发挥重要作用。
