A Dipeptidyl Peptidase-4 Inhibitor Suppresses Macrophage Foam Cell Formation in Diabetic db/db Mice and Type 2 Diabetes Patients
Effects of teneligliptin on foam cell formation and its related gene expression levels in monocyte-derived macrophages isolated from type 2 diabetes (T2D) patients and healthy volunteers. Human peripheral mononuclear cells were isolated from four type 2 diabetes (T2D) patients and four healthy volunteers. Monocytes purified using anti-CD14 antibody-conjugated magnetic microbeads were seeded onto dishes. Adherent monocytes were incubated at 37°C in 5% CO2 for 18 hours with RPMI 1640 medium containing 10% human serum (HS) for 7 days to induce differentiation to macrophages, which were in the presence/absence of 10 nmol/L teneligliptin. (a) Human macrophages differentiated by 7-day culture were incubated at 37°C in 5% CO2 for 18 hours in RPMI 1640 medium containing 10% HS with 10 μg/mL ox-LDL and 0.1 mmol/L [3H] oleate in the presence/absence of 10 nmol/L teneligliptin ex vivo. The cellular lipids were extracted, and the radioactivity of the cholesterol [3H] oleate was determined by thin-layer chromatography. (b-d) Gene expression levels related to foam cell formation in monocyte-derived macrophages isolated from T2D patients and healthy volunteers. Adherent macrophages were incubated at 37°C in 5% CO2 for 18 hours with RPMI 1640 medium containing 10% HS in the presence/absence of 10 nmol/L teneligliptin ex vivo. Gene expression levels of CD36 (b), ACAT-1 (c), and IL-6 (d) and the association with GAPDH were analyzed by real-time RT-PCR without the addition of ox-LDL. Data information: healthy volunteers, T2D patients, and T2D patients with ex vivo teneligliptin treatment after isolation. Results are presented as mean values ± SEM and analyzed with one-way ANOVA: , vs. health volunteers. , vs. T2D patients without ex vivo teneligliptin treatment.
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