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Polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9).
- Source :
-
Cardiovascular diabetology [Cardiovasc Diabetol] 2016 Feb 01; Vol. 15, pp. 19. Date of Electronic Publication: 2016 Feb 01. - Publication Year :
- 2016
-
Abstract
- Background: Abnormalities in lipid and glucose metabolism are constantly observed in type 2 diabetes. However, these abnormalities can be ameliorated by polydatin. Considering the important role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic diseases, we explore the possible mechanism of polydatin on lipid and glucose metabolism through its effects on PCSK9.<br />Methods: An insulin-resistant HepG2 cell model induced by palmitic acid (PA) and a db/db mice model were used to clarify the role of polydatin on lipid and glucose metabolism.<br />Results: In insulin-resistant HepG2 cells, polydatin upregulated the protein levels of LDLR and GCK but repressed PCSK9 protein expression, besides, polydatin also inhibited the combination between PCSK9 and LDLR. Knockdown and overexpression experiments indicated that polydatin regulated LDLR and GCK expressions through PCSK9. In the db/db mice model, we found that polydatin markedly enhanced GCK and LDLR protein levels, and inhibited PCSK9 expression in the liver. Molecular docking assay was further performed to analyze the possible binding mode between polydatin and the PCSK9 crystal structure (PDB code: 2p4e), which indicated that steady hydrogen bonds formed between polydatin and PCSK9.<br />Conclusions: Our study indicates that polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating PCSK9.
- Subjects :
- Animals
Biomarkers blood
Blood Glucose metabolism
Diabetes Mellitus, Type 2 blood
Diabetes Mellitus, Type 2 enzymology
Diabetes Mellitus, Type 2 genetics
Disease Models, Animal
Down-Regulation
Drugs, Chinese Herbal metabolism
Female
Germinal Center Kinases
Glucosides metabolism
Hep G2 Cells
Hepatocytes enzymology
Humans
Hydrogen Bonding
Hypoglycemic Agents metabolism
Lipids blood
Liver enzymology
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Palmitic Acid pharmacology
Proprotein Convertase 9
Proprotein Convertases chemistry
Proprotein Convertases genetics
Protein Binding
Protein Conformation
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
RNA Interference
Receptors, LDL genetics
Receptors, LDL metabolism
Serine Endopeptidases chemistry
Serine Endopeptidases genetics
Stilbenes metabolism
Time Factors
Transfection
Blood Glucose drug effects
Diabetes Mellitus, Type 2 drug therapy
Drugs, Chinese Herbal pharmacology
Glucosides pharmacology
Hepatocytes drug effects
Hypoglycemic Agents pharmacology
Insulin Resistance
Lipid Metabolism drug effects
Liver drug effects
Proprotein Convertases metabolism
Serine Endopeptidases metabolism
Stilbenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2840
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Cardiovascular diabetology
- Publication Type :
- Academic Journal
- Accession number :
- 26833058
- Full Text :
- https://doi.org/10.1186/s12933-015-0325-x