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

PCSK9 and carbohydrate metabolism: A double-edged sword

Theodosios D Filippatos  1 , Sebastian Filippas-Ntekouan  1 , Eleni Pappa  1 , Thalia Panagiotopoulou  1 , Vasilios Tsimihodimos  1 , Moses S Elisaf  1
Affiliations
Editorial

PCSK9 and carbohydrate metabolism: A double-edged sword

Theodosios D Filippatos et al. World J Diabetes. .

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.

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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, SANOFI, BOEHRINGER INGELHEIM, ELI LILLY, GSK. The authors have given talks and attended conferences sponsored by various pharmaceutical companies, including Bristol-Myers Squibb, Pfizer, Lilly, Abbott, Amgen, AstraZeneca, Novartis, Vianex, Teva and MSD.

Figures

Figure 1
Figure 1
The effect of proprotein convertase subtilisin/kexin type 9 (A) and proprotein convertase subtilisin/kexin type 9 inhibition (B) on liver cells low-density lipoprotein receptors expression and serum low-density lipoprotein-cholesterol levels. PCSK9: Proprotein convertase subtilisin/kexin type 9; LDL: Low-density lipoprotein; LDLR: Low-density lipoprotein receptors.
Figure 2
Figure 2
The role of proprotein convertase subtilisin/kexin type 9 on carbohydrate homeostasis. Accordingly, PCSK9 inhibitors may be associated with a neutral effect on carbohydrate homeostasis at least in the short term. PCSK9: Proprotein convertase subtilisin/kexin type 9; LDL: Low-density lipoprotein; LDLR: LDL receptors; HbA1c: Glycated hemoglobin; SREBP-1C: Sterol regulatory element-binding protein I-C; HOMA-IR: Homeostasis model assessment-insulin resistance.
See this image and copyright information in PMC

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