AI Article Synopsis
- * Monoclonal antibodies targeting PCSK9 can significantly lower LDL cholesterol but may also negatively affect glucose metabolism and insulin secretion due to PCSK9's role in pancreatic cells.
- * While clinical trials haven't shown clear negative effects on diabetes risk from PCSK9 inhibitors, their short duration makes it difficult to draw strong conclusions about long-term impacts on carbohydrate metabolism.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507827 | PMC |
| http://dx.doi.org/10.4239/wjd.v8.i7.311 | DOI Listing |
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