PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion.
PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a proprotein convertase that plays a key role in cholesterol homeostasis by decreasing hepatic low-density lipoprotein receptor (LDLR) protein expression. Here, we investigated the expression and the function of PCSK9 in pancreatic islets. Immunohistochemistry analysis showed that PCSK9 co-localized specifically with somatostatin in human pancreatic delta-cells, with no expression in alpha- and beta-cells. PCSK9 seems not to be secreted by mouse isolated islets maintained in culture. Pcsk9-deficiency led to a 200% increase in LDLR protein content in mouse isolated islets, mainly in beta-cells. Conversely, incubation of islets with recombinant PCSK9 almost abolished LDLR expression. However, Pcsk9-deficiency did not alter cholesterol content nor glucose-stimulated insulin secretion in mouse islets. Finally, invivo glucose tolerance was similar in Pcsk9(+/+) and Pcsk9(-/-) mice under basal conditions and following streptozotocin treatment. These results suggest, at least in mice, that PCSK9 does not alter insulin secretion.
Langhi
Cédric
C
INSERM U915, Nantes F-44000, France.
Le May
Cédric
C
Gmyr
Valéry
V
Vandewalle
Brigitte
B
Kerr-Conte
Julie
J
Krempf
Michel
M
Pattou
François
F
Costet
Philippe
P
Cariou
Bertrand
B
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011973:Receptors, LDL / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D019864:Somatostatin-Secreting Cells / Q000187:drug effects / Q000201:enzymology*
D007328:Insulin; D011973:Receptors, LDL; D002784:Cholesterol; C472125:PCSK9 protein, human; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D005947:Glucose