SERCA2b与胰岛β细胞功能

SERCA2b and the function of islet β cells

肌浆（内质）网Ca^2＋ATP酶（SERCAs）是分布于肌浆网或内质网表面重要的Ca^2＋调节蛋白，作为其保守亚型，SERCA2b凭借其独特的结构优势可以保护胰岛β细胞功能，从而在胰岛素正常分泌方面起至关重要的作用。大量研究表明，糖尿病患者体内胰岛8细胞数目明显减少，高糖、炎性因子等因素，通过激活内质网应激降低SERCA2b水平，介导胰岛β细胞损伤和凋亡，此过程可能涉及一氧化氮、AMP活化蛋白激酶（AMPK）、肌醇需求激酶1α（IRE1α）-c-jun氨基末端激酶（JNK）介导的多种信号通路，而提高SERCA2b活性能够逆转损伤，保护胰岛β细胞，改善糖代谢。因此，SERCA2b激动剂也为治疗糖尿病提供了新的方向。

Sarco/endoplasmic reticulum Ca2 ＋ -ATPase （SERCAs） is a series of important Ca2 ＋ reg- ulatory proteins distributed on the surface of the sarcoplasmic reticulum or endoplasmic reticnlum. As conser- vative subtypes, SERCA2b plays a vital role in the function of islet β cell as well as its normally insulin se- cretion relying on its unique structure. A large number of studies have shown that the number of islet β cells is seriously reduced in patients with diabetes. Factors such as high glucose, inflammatory cytokines mediated β cell injury and apoptosis by decreasing SERCA2b level and activating endoplasmic reticulum stress. Nitric oxide（NO） , AMP-activated protein kinase（AMPK） , inositol requiring enzyme-1α/c-jun N-terminal kinase （IRElcx/JNK） pathway may be involved in this process. However, this process can be reversed by impro- ving the activity of SERCA2b and islet β cells are protected at the same time. Therefore, SERCA2b agonist provides a new therapeutic target for treating diabetes.