Display options
Cite
Filippatos TD, Filippas-Ntekouan S, Pappa E, et al. PCSK9 and carbohydrate metabolism: A double-edged sword. World J Diabetes. 2017;8(7):311-316doi: 10.4239/wjd.v8.i7.311.
Filippatos, T. D., Filippas-Ntekouan, S., Pappa, E., Panagiotopoulou, T., Tsimihodimos, V., & Elisaf, M. S. (2017). PCSK9 and carbohydrate metabolism: A double-edged sword. World journal of diabetes, 8(7), 311-316. https://doi.org/10.4239/wjd.v8.i7.311
Filippatos, Theodosios D, et al. "PCSK9 and carbohydrate metabolism: A double-edged sword." World journal of diabetes vol. 8,7 (2017): 311-316. doi: https://doi.org/10.4239/wjd.v8.i7.311
Filippatos TD, Filippas-Ntekouan S, Pappa E, Panagiotopoulou T, Tsimihodimos V, Elisaf MS. PCSK9 and carbohydrate metabolism: A double-edged sword. World J Diabetes. 2017 Jul 15;8(7):311-316. doi: 10.4239/wjd.v8.i7.311. PMID: 28751953; PMCID: PMC5507827.
Copy Download .nbib Format: NLM
Share it on

World J Diabetes. 2017 Jul 15;8(7):311-316. doi: 10.4239/wjd.v8.i7.311.

PCSK9 and carbohydrate metabolism: A double-edged sword.

World journal of diabetes

Theodosios D Filippatos, Sebastian Filippas-Ntekouan, Eleni Pappa, Thalia Panagiotopoulou, Vasilios Tsimihodimos, Moses S Elisaf

Affiliations

  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.

PMID: 28751953 PMCID: PMC5507827 DOI: 10.4239/wjd.v8.i7.311

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.

Keywords: Carbohydrate metabolism; Diabetes; Low-density lipoprotein; Proprotein convertase subtilisin/kexin type 9; Proprotein convertase subtilisin/kexin type 9 inhibitors

Conflict of interest statement

Conflict-of-interest statement: This review was written independently. Professor Elisaf MS reports personal fees from ASTRA ZENECA, grants and personal fees from MSD, personal fees from PFIZER, ABBOTT

References

  1. Trends Biochem Sci. 2007 Feb;32(2):71-7 - PubMed
  2. N Engl J Med. 2016 Dec;375(22):2144-2153 - PubMed
  3. Clin Chem. 2009 Sep;55(9):1637-45 - PubMed
  4. JAMA. 2011 Jun 22;305(24):2556-64 - PubMed
  5. Curr Cardiol Rep. 2013 Mar;15(3):345 - PubMed
  6. J Lipid Res. 2010 Nov;51(11):3342-9 - PubMed
  7. Lancet Diabetes Endocrinol. 2016 May;4(5):403-10 - PubMed
  8. JAMA. 2016 Oct 4;316(13):1383-1391 - PubMed
  9. Atherosclerosis. 2014 Oct;236(2):321-6 - PubMed
  10. N Engl J Med. 2006 Mar 23;354(12 ):1264-72 - PubMed
  11. Lancet. 2010 Feb 27;375(9716):735-42 - PubMed
  12. FEBS Lett. 2010 Feb 19;584(4):701-6 - PubMed
  13. Lancet. 2015 Jan 24;385(9965):351-61 - PubMed
  14. Atherosclerosis. 2010 Aug;211(2):700-2 - PubMed
  15. Diabetologia. 2015 Sep;58(9):2051-5 - PubMed
  16. Eur Heart J. 2016 Feb 7;37(6):536-45 - PubMed
  17. J Biol Chem. 2006 Mar 10;281(10 ):6211-8 - PubMed
  18. Eur Heart J. 2016 Oct 14;37(39):2981-2989 - PubMed
  19. Can J Cardiol. 2013 Aug;29(8):927-33 - PubMed
  20. Diabetes Obes Metab. 2017 Jan;19(1):98-107 - PubMed
  21. N Engl J Med. 2008 Nov 20;359(21):2195-207 - PubMed
  22. Lancet Diabetes Endocrinol. 2017 Feb;5(2):97-105 - PubMed
  23. Biochem Biophys Res Commun. 2009 Dec 25;390(4):1288-93 - PubMed
  24. Curr Opin Lipidol. 2009 Jun;20(3):159-64 - PubMed

Publication Types