Journal
BIOMEDICINES
Volume 9, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines9070832
Keywords
GIP; CD36; Cdk5; GIP receptor; macrophages
Categories
Funding
- JSPS KAKENHI [20K07075, 20K06475]
- Grants-in-Aid for Scientific Research [20K06475, 20K07075] Funding Source: KAKEN
Ask authors/readers for more resources
The study suggests that GIP may inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor.
Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and CD36 expression in, macrophages extracted from GIP receptor-deficient (Gipr(-/-)) and Gipr(+/+) mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala(2)]GIP(1-42). Foam cell formation evaluated by esterification of free cholesterol to cholesteryl ester and CD36 gene expression in macrophages isolated from Gipr(+/+) mice infused subcutaneously with [D-Ala(2)]GIP(1-42) were significantly suppressed compared with vehicle-treated mice, while these beneficial effects were not observed in macrophages isolated from Gipr(-/-) mice infused with [D-Ala(2)]GIP(1-42). When macrophages were isolated from Gipr(+/+) and Gipr(-/-) mice, and then exposed to [D-Ala(2)]GIP(1-42), similar results were obtained. [D-Ala(2)]GIP(1-42) attenuated ox-LDL uptake of, and CD36 gene expression in, human U937 macrophages as well. Gene expression level of cyclin-dependent kinase 5 (Cdk5) was also suppressed by [D-Ala(2)]GIP(1-42) in U937 cells, which was corelated with that of CD36. A selective inhibitor of Cdk5, (R)-DRF053 mimicked the effects of [D-Ala(2)]GIP(1-42) in U937 cells. The present study suggests that GIP could inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available