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PCSK9 and carbohydrate metabolism: A double-edged sword.

Authors
  • Filippatos, Theodosios D1
  • Filippas-Ntekouan, Sebastian1
  • Pappa, Eleni1
  • Panagiotopoulou, Thalia1
  • Tsimihodimos, Vasilios1
  • Elisaf, Moses S1
  • 1 Theodosios D Filippatos, Sebastian Filippas-Ntekouan, Eleni Pappa, Thalia Panagiotopoulou, Vasilios Tsimihodimos, Moses S Elisaf, Department of Internal Medicine, School of Medicine, University of Ioannina, 45110 Ioannina, Greece. , (Greece)
Type
Published Article
Journal
World Journal of Diabetes
Publisher
Baishideng Publishing Group Co (World Journal of Diabetes)
Publication Date
Jul 15, 2017
Volume
8
Issue
7
Pages
311–316
Identifiers
DOI: 10.4239/wjd.v8.i7.311
PMID: 28751953
Source
Medline
Keywords
License
Unknown

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a paramount role in the degradation of low-density lipoprotein (LDL) receptors (LDLR) on the hepatic cells surface and subsequently affects LDL particles catabolism and LDL cholesterol (LDL-c) levels. The anti-PCSK9 monoclonal antibodies lead to substantial decrease of LDL-c concentration. PCSK9 (which is also expressed in pancreatic delta-cells) can decrease LDLR and subsequently decrease cholesterol accumulation in pancreatic beta-cells, which impairs glucose metabolism and reduces insulin secretion. Thus, a possible adverse effect of PCSK9 inhibitors on carbohydrate metabolism may be expected by this mechanism, which has been supported by the mendelian studies results. On the other hand, clinical data have suggested a detrimental association of PCSK9 with glucose metabolism. So, the inhibition of PCSK9 may be seen as a double-edged sword regarding carbohydrate metabolism. Completed clinical trials have not shown a detrimental effect of PCSK9 inhibitors on diabetes risk, but their short-term duration does not allow definite conclusions.

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