近期《自然—细胞生物学》上的一项报告揭示了内质网（ER）应激信号与胰岛素产生、分泌之间的一种联系。该发现为糖尿病治疗研究的发展提供了新的机遇。
WFS1基因的突变可导致沃尔弗拉姆（Wolfram）综合征的产生，该综合征以儿童期糖尿病为特点；WFS1基因已被证实可以调控ER应激信号从而干扰正常的ER蛋白折叠功能，此外，WFS1还是生产胰岛素的胰腺β细胞维持正常功能所必需的。
Sonya Fonseca等人报告称WFS1在调节小鼠体内胰腺β细胞的胰岛素释放方面具有更深层次的作用。进食后生物体内血液中富集的葡萄糖能促使WFS1移动到细胞膜处以刺激胰岛素的产生和分泌。研究人员表示，WFS1的高水平表达能够恢复由于ER应激而受影响的胰腺β细胞的胰岛素分泌。由此，他们认为WFS1或可作为新型糖尿病疗法中的一个重要靶点。（生物谷Bioon.com）
doi:10.1038/ncb2578
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Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to regulate insulin production and secretion
Sonya G. Fonseca, Fumihiko Urano, Gordon C. Weir, Jesper Gromada & Mark Burcin
Endoplasmic reticulum (ER) stress causes pancreatic β-cell dysfunction and contributes to β-cell loss and the progression of type 2 diabetes1, 2. Wolfram syndrome 1 (WFS1) has been shown to be an important regulator of the ER stress signalling pathway3; however, its role in β-cell function remains unclear. Here we provide evidence that WFS1 is essential for glucose- and glucagon-like peptide 1 (GLP-1)-stimulated cyclic AMP production and regulation of insulin biosynthesis and secretion. Stimulation with glucose causes WFS1 translocation from the ER to the plasma membrane, where it forms a complex with adenylyl cyclase 8 (AC8), an essential cAMP-generating enzyme in the β-cell that integrates glucose and GLP-1 signalling4. ER stress and mutant WFS1 inhibit complex formation and activation of AC8, reducing cAMP synthesis and insulin secretion. These findings reveal that an ER-stress-related protein has a distinct role outside the ER regulating both insulin biosynthesis and secretion. The reduction of WFS1 protein on the plasma membrane during ER stress is a contributing factor for β-cell dysfunction and progression of type 2 diabetes.
