Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
FEBS Lett. 2010 Feb 19;584(4):701-6. doi: 10.1016/j.febslet.2009.12.018. Epub 2009 Dec 16.
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a liver-secreted plasma enzyme, restricts hepatic uptake of low-density lipoprotein (LDL) cholesterol by promoting the degradation of LDL receptors (LDLR). PCSK9 and LDLR are also expressed in insulin-producing pancreatic islet beta cells, possibly affecting the function of these cells. Here we show that, compared to control mice, PCSK9-null male mice over 4 months of age carried more LDLR and less insulin in their pancreas; they were hypoinsulinemic, hyperglycemic and glucose-intolerant; their islets exhibited signs of malformation, apoptosis and inflammation. Collectively, these observations suggest that PCSK9 may be necessary for the normal function of pancreatic islets.
前蛋白转化酶枯草溶菌素 9（PCSK9）是一种肝脏分泌的血浆酶，通过促进 LDL 受体（LDLR）的降解来限制肝脏对 LDL 胆固醇的摄取。PCSK9 和 LDLR 也在产生胰岛素的胰岛β细胞中表达，可能影响这些细胞的功能。在这里，我们发现与对照组小鼠相比，4 个月以上的 PCSK9 缺失雄性小鼠的胰腺中 LDLR 更多，而胰岛素更少；它们表现出低血糖、高血糖和葡萄糖不耐受；其胰岛出现了畸形、凋亡和炎症的迹象。综上所述，这些观察结果表明 PCSK9 可能是胰岛正常功能所必需的。
