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PCSK9 and carbohydrate metabolism: A double-edged sword

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 le...

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Autores principales: Filippatos, Theodosios D, Filippas-Ntekouan, Sebastian, Pappa, Eleni, Panagiotopoulou, Thalia, Tsimihodimos, Vasilios, Elisaf, Moses S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507827/
https://www.ncbi.nlm.nih.gov/pubmed/28751953
http://dx.doi.org/10.4239/wjd.v8.i7.311
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author Filippatos, Theodosios D
Filippas-Ntekouan, Sebastian
Pappa, Eleni
Panagiotopoulou, Thalia
Tsimihodimos, Vasilios
Elisaf, Moses S
author_facet Filippatos, Theodosios D
Filippas-Ntekouan, Sebastian
Pappa, Eleni
Panagiotopoulou, Thalia
Tsimihodimos, Vasilios
Elisaf, Moses S
author_sort Filippatos, Theodosios D
collection PubMed
description 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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spelling pubmed-55078272017-07-28 PCSK9 and carbohydrate metabolism: A double-edged sword Filippatos, Theodosios D Filippas-Ntekouan, Sebastian Pappa, Eleni Panagiotopoulou, Thalia Tsimihodimos, Vasilios Elisaf, Moses S World J Diabetes Editorial 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. Baishideng Publishing Group Inc 2017-07-15 2017-07-15 /pmc/articles/PMC5507827/ /pubmed/28751953 http://dx.doi.org/10.4239/wjd.v8.i7.311 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Editorial
Filippatos, Theodosios D
Filippas-Ntekouan, Sebastian
Pappa, Eleni
Panagiotopoulou, Thalia
Tsimihodimos, Vasilios
Elisaf, Moses S
PCSK9 and carbohydrate metabolism: A double-edged sword
title PCSK9 and carbohydrate metabolism: A double-edged sword
title_full PCSK9 and carbohydrate metabolism: A double-edged sword
title_fullStr PCSK9 and carbohydrate metabolism: A double-edged sword
title_full_unstemmed PCSK9 and carbohydrate metabolism: A double-edged sword
title_short PCSK9 and carbohydrate metabolism: A double-edged sword
title_sort pcsk9 and carbohydrate metabolism: a double-edged sword
topic Editorial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507827/
https://www.ncbi.nlm.nih.gov/pubmed/28751953
http://dx.doi.org/10.4239/wjd.v8.i7.311
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