Romere Chase, Duerrschmid Clemens, Bournat Juan, Constable Petra, Jain Mahim, Xia Fan, Saha Pradip K, Del Solar Maria, Zhu Bokai, York Brian, Sarkar Poonam, Rendon David A, Gaber M Waleed, LeMaire Scott A, Coselli Joseph S, Milewicz Dianna M, Sutton V Reid, Butte Nancy F, Moore David D, Chopra Atul R
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Cell. 2016 Apr 21;165(3):566-79. doi: 10.1016/j.cell.2016.02.063. Epub 2016 Apr 14.
Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.
在禁食期间，肝脏向循环系统释放葡萄糖对于大脑功能和生存至关重要，并且受到一系列精确调节血糖水平的激素的调控。我们已经鉴定出一种禁食诱导的蛋白质激素，它可调节肝脏葡萄糖释放。它是原纤连蛋白的C末端裂解产物，我们将其命名为阿朴脂蛋白。阿朴脂蛋白由白色脂肪分泌，以纳摩尔水平循环，并被募集到肝脏，在那里它激活G蛋白 - cAMP - PKA途径，导致葡萄糖迅速释放到循环系统中。患有胰岛素抵抗的人类和小鼠表现出血浆阿朴脂蛋白病理性升高，通过免疫或基因手段使其功能丧失会因肝脏葡萄糖释放减少而产生显著的降血糖和降胰岛素作用。阿朴脂蛋白代表一种生糖蛋白激素，以其为治疗靶点可能对II型糖尿病和代谢综合征有益。
