Premium
PCSK9‐deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities
Author(s) -
Mbikay Majambu,
Sirois Francine,
Mayne Janice,
Wang Gen-Sheng,
Chen Andrew,
Dewpura Thilina,
Prat Annik,
Seidah Nabil G.,
Chretien Michel,
Scott Fraser W.
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.12.018
Subject(s) - medicine , endocrinology , pcsk9 , kexin , ldl receptor , islet , pancreas , insulin , proprotein convertase , biology , pancreatic islets , cholesterol , lipoprotein
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.