The Effect Of Exendin-4 On The Endothelial Progenitor Cells Function And AKT/eNOS Signaling Pathway In A Mouse Model Of Type 1 Diabetes

Background:Bone marrow-derived endothelial progenitor cells(EPCs)play a key role in vascular repair and angiogenesis.Dysfunction of EPCs contribute to the development of cardiovascular complication in diabetes.However,the effects of Exendin-4 on EPCs and the underlying mechanisms have not been reported.Herein,we attempted to elucidate the function and mechanism of Exendin-4 on regulating EPCs in a modle of type Ⅰ diabetic mice.Objective: The prupose of this study was to justify the effects of Exendin-4 on proliferation,migration,adhesion and senescence of EPCs in type Ⅰ diabetic mice and its possible mechanism.Methods: EPCs from 6-months diabetic mice were isolated and cultured by density gradient centrifugation.Cells were treated with different concentrations of Exendin-4(1 uM,5 uM,10 uM,25 uM)for 7 days to observe the proliferation capacity in vitro.The effects of Exendin-4 on the migration,adhesion and senescence of EPCs were also observed.The effect of Exendin-4 on the signaling pathway of protein kinase B/endothelial nitric oxide synthetase(AKT/eNOS)was detected by Western blot.Results: Exendin-4 could increase the proliferation ability of EPCs in type Ⅰ diabetic mice in a dose-dependent manner,especially for 10 uM.Compared with the control group,the treatment of 10 uM Exendin-4 could increase the migration and adhesion function of EPCs in vitro,and inhibit cell senescence.The results of Western blot showed that the phosphorylation of AKT and eNOS was significantly enhanced by10 uM of Exendin-4 treatment,which was blocked by the GLP-1R inhibitor Exendin-9-39 and the AKT inhibitor MK-2206.Conclusions : Exendin-4 can improve the proliferation,migration,adhesion capacities and inhibit senescence of EPCs in type Ⅰ diabetic mice,which may be related to the regulation of AKT/eNOS signaling pathway.