Roles of plasma membrane ryanodine receptors in pancreatic beta cells.

2型糖尿病，正如它的另一个名字（成熟型糖尿病）所暗示的那样，曾经是老年人的疾病。但肥胖是2型糖尿病的主要诱发因素，在所有年龄组中都在惊人地增加，2型糖尿病的患病率也是如此，自2000年以来，西方国家的2型糖尿病患者至少增加了25%，其他地区的2型糖尿病患者增加了50%或更多。糖尿病需要终生治疗，其并发症会降低生活质量和预期寿命。当胰腺中的β细胞不再能够释放足够的胰岛素来有效控制血糖浓度时，就会出现这种疾病。大多数用于治疗糖尿病的药物通过促进胰岛素释放起作用，但它们不能忠实地复制胰岛素分泌的振荡变化，而胰岛素分泌对靶组织的葡萄糖摄取提供了最有效的调节。我们的工作已经在包围β细胞的膜中发现了一个通道（2型ryanodine受体，RyR2）。我们认为，当释放胰岛素的囊泡与胰岛素融合时，RyR2可能被插入到该膜中，然后RyR2可能控制调节胰岛素释放的钙离子的通量。因此，RyR2的这种意想不到的贡献可能构成了促进胰岛素释放振荡控制的调节回路的一部分。RyR2的可及性（在细胞表面）可能使其成为促进胰岛素释放的新药的靶标。我们的工作涉及揭示RyR2在控制胰岛素释放中的作用。

Type 2 diabetes, as its alternative name (maturity-onset diabetes) suggests, was once a disease of older people. But obesity, the major pre-disposing factor for type 2 diabetes, is increasing alarmingly among all age-groups and so too is the prevalence of type 2 diabetes, which increased by at least 25% in the west and by 50% or more elsewhere since 2000. Diabetes requires lifelong therapy and its complications reduce quality or life and life-expectancy. The disease presents when beta-cells in the pancreas are no longer able to release sufficient insulin to control effectively the blood glucose concentration. Most drugs used to treat diabetes work by promoting insulin release, but they cannot faithfully replicate the oscillatory changes in insulin secretion that provide the most effective regulation of glucose uptake by target tissues. Our work has identified a channel (the type 2 ryanodine receptor, RyR2) in the membrane that surrounds the beta-cell. We suggest that RyR2 may be inserted into this membrane when the vesicles that release insulin fuse with it, and that the RyR2 may then control the flux of calcium ions that regulates insulin release. This unexpected contribution from RyR2 may thereby form part of a regulatory loop contributing to oscillatory control of insulin release. The accessibility of RyR2 (on the surface of the cell) may allow it to become a target for novel drugs to promote insulin release. Our work is concerned with unravelling the roles of RyR2 in control of insulin release.