title: PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities.
abstract: 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.
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. mmbikay@ohri.ca
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay
authors.forename: Francine
authors.initials: F
authors.lastname: Sirois
authors.forename: Janice
authors.initials: J
authors.lastname: Mayne
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Chen
authors.forename: Thilina
authors.initials: T
authors.lastname: Dewpura
authors.forename: Annik
authors.initials: A
authors.lastname: Prat
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Michel
authors.initials: M
authors.lastname: Chretien
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D018149:Glucose Intolerance / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007515:Islets of Langerhans / Q000002:abnormalities / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics*; D046509:Tissue Culture Techniques
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011973:Receptors, LDL; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases