Study on the Function Change of Caco-2 Cell CYP3A4 and P-gp under Diabetic Conditions and Its Mecha-nism
10.6039/j.issn.1001-0408.2016.25.05
- VernacularTitle:糖尿病状态下Caco-2细胞CYP3A4和P-gp功能的变化及其机制研究Δ
- Author:
Sulan ZOU
;
Nan HU
- Publication Type:Journal Article
- Keywords:
Diabetes;
Caco-2 cells;
CYP3A4;
P-glycoprotein;
Insulin;
Glucose;
Fatty acid;
in vitro test
- From:
China Pharmacy
2016;27(25):3471-3474
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the function change of intestinal CYP3A4 and P-glycoprotein (P-gp) under diabetic conditions and its mechanism. METHODS:Caco-2 cells were respectively added with 25, 50 and 100 μmol/L midazolam (CYP3A4 probe substrate) for incubation for 15,30,60,120,180 min;with 0.1,0.2,0.4 μg/ml rhodamine 123 (P-gp sub-strate)for incubation for 15,30,60,90,120 min to determine the substrate concentrations and incubation time. Caco-2 cells were added with insulin,glucose and fatty acid (palmitic acid and oleic acid) at different concentrations,and then the production of 1′-OH-midazolam,the metabolite of midazolam,and the intake of rhodamine 123 were determined,in order to investigated the ef-fect on the function of CYP3A4 and P-gp. RESULTS:The optimal substrate concentrations and incubation time were as follows as 50 μmol/L midazolam,0.1 μg/ml rhodamine 123 and incubation for 2 h. With the increase in the concentration of insulin,glucose and palmitic acid,the production of 1′-OH-midazolam and the activity of CYP3A4 reduced;the intake of rhodamine 123 in-creased,and the efflux transport function of P-gp decreased. Oleic acid had no significant effect on the production of 1′-OH-mid-azolam or the intake of rhodamine 123. CONCLUSIONS:Under diabetes condition,the increase of insulin,glucose and palmitic acid may reduce the function of CYP3A4 and P-gp,while oleic acid has no effect on the function.
