| RRC ID |
82112
|
| 著者 |
Komatsu T, Abe S, Nakashima S, Sasaki K, Higaki Y, Saku K, Miura SI, Uehara Y.
|
| タイトル |
Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Phosphate Accelerates Cellular Cholesterol Efflux in THP-1 Cells.
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| ジャーナル |
Biomolecules
|
| Abstract |
Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with 3H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly (p < 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux.
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| 巻・号 |
13(2)
|
| 公開日 |
2023-1-24
|
| DOI |
10.3390/biom13020228
|
| PII |
biom13020228
|
| PMID |
36830597
|
| PMC |
PMC9953524
|
| MeSH |
Cholesterol / metabolism
Diabetes Mellitus, Type 2* / metabolism
Dipeptidyl-Peptidase IV Inhibitors*
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Glucagon-Like Peptide 1 / metabolism
Humans
Hypoglycemic Agents
Sitagliptin Phosphate
THP-1 Cells
|
| IF |
4.082
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189) |
