The dipeptidyl peptidase 4 (DPP4) is a protein that presenting in various cells of the body and is associated with immune regulation, glucose metabolism and cardiovascular function[3]. Sitagliptin, which is used to treat diabetes, is a DPP4 inhibitor with IC50 value of 19 nM[4]. HLMVECs were treated with sitagliptin with 1000 μM for one hour and the DPP4 activity measured using a CD26/DPPIV Assay kit after four hours of PBS incubation was decreased significantly compared with the control group. The secreated cytokine levels detected by ELISA after LPS (1 μg/ml) for four hours was decreased significantly compared with the cells without sitagliptin treatment[5]. When sitagliptin was treated with LPS treated (10 μg/ml) H9c2 cells with concentration of 1 μM and above, the cytokines level measured by PCR and ELISA also decreased siginificantly compared with control. The NF-kB level measured by western blotting assay also decreased significantly[6]. In high salt diet Dahl salt-sensitive rats, sitagliptin was given to the rats orally daily with 10 mg/ kg for eight weeks. The survival rate of the sitagliptin treated group was higher than the control group, and the in situ assessment of DPP4 activity was reduced coupled with an increased expression of GLP-1 receptors from sitagliptin treated group, measured by immunofluorescence labelling and confocal microscopy[7].
作用机制
The sitagliptin is a competitive, tight and fast binding inhibitor to the DPP4. It can prolong the bioactivity of the native GLP-1 by inhibiting the proteolytic activity of the DPP4 enzyme[8].
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