Asprosin, a Fasting-Induced Glucogenic Protein Hormone.
Asprosin, a Fasting-Induced Glucogenic Protein Hormone.
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DOI：
10.1016/j.cell.2016.02.063
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发表时间：
2016-04-21
期刊：
影响因子：
64.5
通讯作者：
Chopra AR
中科院分区：
文献类型：
--
作者：
Romere C;Duerrschmid C;Bournat J;Constable P;Jain M;Xia F;Saha PK;Del Solar M;Zhu B;York B;Sarkar P;Rendon DA;Gaber MW;LeMaire SA;Coselli JS;Milewicz DM;Sutton VR;Butte NF;Moore DD;Chopra AR
肝脏葡萄糖释放到循环中对禁食期间的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节。我们已经确定了一个禁食诱导的蛋白激素，调节肝脏葡萄糖的释放。它是脯氨酸的C-末端裂解产物，我们将其命名为Asprosin。白色脂肪肽由白色脂肪分泌，以纳摩尔水平循环，并被募集到肝脏，在肝脏中激活G蛋白-cAMP-PKA途径，导致葡萄糖快速释放到循环中。具有胰岛素抵抗的人类和小鼠显示出病理性血浆白色脂肪肽升高，并且其通过免疫学或遗传学方式的功能丧失具有继发于肝脏葡萄糖释放减少的显著的葡萄糖和胰岛素降低作用。白色脂肪肽代表一种生糖蛋白激素，治疗靶向它可能对II型糖尿病和代谢综合征有益。
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.