PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion

Biochem Biophys Res Commun. 2009 Dec 25;390(4):1288-93. doi: 10.1016/j.bbrc.2009.10.138. Epub 2009 Oct 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cholesterol / metabolism
  • Glucose / metabolism
  • Glucose / pharmacology
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Receptors, LDL / metabolism
  • Serine Endopeptidases / biosynthesis*
  • Serine Endopeptidases / genetics
  • Somatostatin-Secreting Cells / drug effects
  • Somatostatin-Secreting Cells / enzymology*

Substances

  • Insulin
  • Receptors, LDL
  • Cholesterol
  • PCSK9 protein, human
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases
  • Glucose