Journal Article Review Research Support, Non-U.S. Gov't Ppublish 11 citations
PubMed: 35723066 DOI: 10.1080/1061186X.2022.2092622
Molecular and cellular biology of PCSK9: impact on glucose homeostasis.
J Drug Target 30(9):948-960
Authors: Sègbédé E R Tchéoubi, Casimir D Akpovi, Frédérique Coppée, Anne-Emilie Declèves, Sophie Laurent, Clément Agbangla, Carmen Burtea
Affiliations
- General, Organic and Biomedical Chemistry Unit, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Mons, Belgium. Non-Communicable Diseases and Cancer Research Unit, Laboratory of Applied Biology Research, University of Abomey-Calavi - UAC, Abomey-Calavi, Benin.
- Non-Communicable Diseases and Cancer Research Unit, Laboratory of Applied Biology Research, University of Abomey-Calavi - UAC, Abomey-Calavi, Benin.
- Laboratory of Metabolic and Molecular Biochemistry, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Mons, Belgium.
- General, Organic and Biomedical Chemistry Unit, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Mons, Belgium.
- Laboratory of Molecular Genetics and Genome Analyzes, Faculty of Sciences and Technics, University of Abomey-Calavi - UAC, Abomey-Calavi, Benin.
Abstract
Proprotein convertase substilisin/kexin 9 (PCSK9) inhibitors (PCSK9i) revolutionised the lipid-lowering therapy. However, a risk of type 2 diabetes mellitus (T2DM) is evoked under PCSK9i therapy. In this review, we summarise the current knowledge on the link of PCSK9 with T2DM. A significant correlation was found between PCSK9 and insulin, homeostasis model assessment (HOMA) of insulin resistance and glycated haemoglobin. PCSK9 is also involved in inflammation. PCSK9 loss-of-function variants increased T2DM risk by altering insulin secretion. Local pancreatic low PCSK9 regulates β-cell LDLR expression which in turn promotes intracellular cholesterol accumulation and hampers insulin secretion. Nevertheless, the association of PCSK9 loss-of-function variants and T2DM is inconsistent. InsLeu and R46L polymorphisms were associated with T2DM, low HOMA for β-cell function and impaired fasting glucose, while the C679X polymorphism was associated with low fasting glucose in Black South African people. Hence, we assume that the impact of these variants on glucose homeostasis may vary depending on the genetic background of the studied populations and the type of effect caused by those genetic variants on the PCSK9 protein. Accordingly, these factors should be considered when choosing a genetic variant of PCSK9 to assess the impact of long-term use of PCSK9i on glucose homeostasis.
MeSH
Diabetes Mellitus, Cells, Fasting, Insulin, Homeostasis, Cardiovascular Diseases, Insulin Secretion, Cell Biology, Drug Delivery Systems, Therapeutics, Drug Evaluation, Diabetes Mellitus, Type 2
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- PCSK9 inhibition and cholesterol homeostasis in insulin producing β-cells. Lipids Health Dis, 2022
- Geranylgeranyl isoprenoids and hepatic Rap1a regulate basal and statin-induced expression of PCSK9. J Lipid Res, 2024
- Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study. Front Endocrinol (Lausanne), 2023
- Bridging epigenetics and pharmacology through systematic reviews tailored to WBS methodology: the triangle decision-making model as a pioneering translational biological drug delivery system. Front Med (Lausanne), 2025