胰島β細(xì)胞表達(dá)生成的PICK1和胰島素顆粒合并在一起

胰島素是調(diào)節(jié)血糖的主要激素，胰島素分泌不足會(huì)造成糖尿病。胰島素的前體是胰島素原，通過(guò)內(nèi)質(zhì)網(wǎng)和高爾基體的加工，zui終被包裹形成胰島素顆粒。胰島素顆粒是一種致密的核心囊泡。但是胰島素顆粒的生物合成和成熟的分子機(jī)制依然不是很清楚。

在該研究中，研究人員發(fā)現(xiàn)了兩個(gè)包漿蛋白PICK1 和 ICA69，它們被認(rèn)為參與調(diào)節(jié)胰島素顆粒的生物合成和成熟加工。PICK1和ICA69都有一個(gè)香蕉形的BAR結(jié)構(gòu)域，這個(gè)結(jié)構(gòu)域可以彎曲脂質(zhì)膜，促進(jìn)致密核心囊泡的成熟加工。

研究表明，如果缺少了PICK1 和 ICA69兩者中的任何一種，胰島素顆粒就不能順利的形成，這樣導(dǎo)致的結(jié)果就是，胰島素原不能轉(zhuǎn)變成成熟的胰島素。缺乏PICK1 或者 ICA69基因的小鼠，它們的血糖會(huì)升高，這在糖尿病患者中也是一個(gè)很顯著的特點(diǎn)。所以，結(jié)合以往的研究表明，PICK1對(duì)于顆粒的形成非常重要，同時(shí)PICK1 和 ICA69在調(diào)節(jié)致密核心囊泡的生物合成和成熟中發(fā)揮著非常重要的作用。

PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance

Mian Cao equal contributor, Zhuo Mao equal contributor, Chuen Kam, Nan Xiao, Xiaoxing Cao, Chong Shen, Kenneth K. Y. Cheng, Aimin Xu, Kwong-Man Lee, Liwen Jiang,Jun Xia

Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network （TGN）. A brief treatment of Brefeldin A