PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities

详细信息    查看全文

• 作者：Majambu Mbikay ; Francine Sirois ; Janice Mayne ; Gen-Sheng Wang ; Andrew Chen ; Thilina Dewpura ; Annik Prat ; Nabil G. Seidah ; Michel Chretien ; Fraser W. Scott
• 关键词：Proprotein convertase ; Pancreatic islet beta cell ; Cholesterol ; low-density lipoprotein ; Glucose
• 刊名：FEBS Letters
• 出版年：2010
• 出版时间：19 February 2010
• 年：2010
• 卷：584
• 期：4
• 页码：701-706
• 全文大小：4795 K

文摘

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 β 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.