近日，来自美国的科学家发现了触发胰腺beta细胞再生的新途径，这一关键进展将有助于糖尿病治疗方法的开发。相关研究结果发表在国际学术期刊JCI 上。
胰岛素是由胰腺beta细胞分泌产生的一种调节血糖水平的激素。当机体对胰岛素的需求超过beta细胞的胰岛素合成能力，比如beta细胞损失（1型糖尿病）和体重增加（2型糖尿病），beta细胞就会进行增殖以增加细胞数量。但直到现在，仍然不清楚beta细胞如何感应机体需求以合成更多胰岛素。
在这项研究中，研究人员对于胰腺如何知道机体需要更多合成胰岛素的beta细胞进行了深入研究。他们发现当胰岛素需求增加，beta细胞内质网内胰岛素的合成就会相应增加，这会引起一些内质网应激。
研究人员指出，虽然之前许多研究已经发现太多的内质网应激对beta细胞有害，造成beta细胞死亡，但这项研究发现适度的应激对beta细胞是有好处的，这样会为机体提供一些压力以增加beta细胞数目，合成更多胰岛素，进而维持血糖平衡。
同时，这项研究还发现内质网应激途径会通过一种叫做ATF6的内质网蛋白向细胞核内发送信号，告诉细胞要进行增殖。更为重要的是，这项研究还发现这条途径的一些关键组成部分在人类beta细胞中也活跃表达。
总的来说，这些研究结果表明beta细胞需要感受应激以确定机体还需要多少beta细胞进行胰岛素合成，因此beta细胞对应激非常敏感。并且只有完全成熟的能够合成胰岛素的beta细胞才能应用这种应激机制感受机体对胰岛素的需求。
Insulin demand regulates β cell number via the unfolded protein response
Rohit B. Sharma1, Amy C. O'Donnell2, Rachel E. Stamateris1, Binh Ha1, Karen M. McCloskey2, Paul R. Reynolds3, Peter Arvan4, and Laura C. Alonso
Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic β cell number expands in response to an increase in insulin demand. Lineage tracing shows that new β cells are generated from proliferation of mature, differentiated β cells; however, the mechanism by which these mature cells sense systemic insulin demand and initiate a proliferative response remains unknown. Here, we identified the β cell unfolded protein response (UPR), which senses insulin production, as a regulator of β cell proliferation. Using genetic and physiologic models, we determined that among the population of β cells, those with an active UPR are more likely to proliferate. Moreover, subthreshold endoplasmic reticulum stress (ER stress) drove insulin demand-induced β cell proliferation, through activation of ATF6. We also confirmed that the UPR regulates proliferation of human β cells, suggesting that therapeutic UPR modulation has potential to expand β cell mass in people at risk for diabetes. Together, this work defines a stem cell-independent model of tissue homeostasis, in which differentiated secretory cells use the UPR sensor to adapt organ size to meet demand.