Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov;57(11):1315-1326.
doi: 10.1007/s00592-020-01551-3. Epub 2020 Jun 16.

Exendin-4 reverses high glucose-induced endothelial progenitor cell dysfunction via SDF-1β/CXCR7-AMPK/p38-MAPK/IL-6 axis

Yong Yang #  1   2 , Yong Zhou #  3 , Yiyong Wang  4 , Xianglong Wei  2 , Lihao Wu  5 , Tingzhong Wang  1   6   7 , Aiqun Ma  8   9   10
Affiliations

Exendin-4 reverses high glucose-induced endothelial progenitor cell dysfunction via SDF-1β/CXCR7-AMPK/p38-MAPK/IL-6 axis

Yong Yang et al. Acta Diabetol. 2020 Nov.

Abstract

Aim: Exendin-4, a glucagon-like peptide-1 (GLP-1) analog, has been used for treating diabetes mellitus (DM). However, its effects on improving the dysfunction of high glucose (HG)-induced endothelial progenitor cells (EPCs) remain unclear. The present study explored the effects of Exendin-4 on improving dysfunction of EPCs and the underlying mechanism.

Methods: EPCs were isolated from SD rats and identified by flow cytometry. Next, the EPCs were treated by HG and high or low concentration of Exendin-4, and cell viability, migration and tube formation were, respectively, examined by performing MTT assay, wound-healing assay and tube formation assay. Interleukin-6 (IL-6) secretion was measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of relative stromal-derived growth factor-1β (SDF-1β), C-X-C chemokine receptor type 7 (CXCR7), AMP-activated protein kinase (AMPK), p38 and expressions of CXCR7 and IL-6 in EPCs were measured by Western blot. The cell behaviors of EPCs treated by HG and Exendin-4 with or without silencing of CXCR7 and IL-6 were detected.

Results: Exendin-4 reversed the inhibitory effects of HG on viability, migration and tube formation of EPCs and on SDF-1β/CXCR7-AMPK pathway in EPCs in a dose-dependent manner. Moreover, Exendin-4 promoted the effects of HG on IL-6 level in EPCs through the promotion of p38-MAPK phosphorylation and reduction of cleaved caspase-3 protein expressions in EPCs. However, silencing of CXCR7 and IL-6 reversed the effects of Exendin-4 on cell behaviors, inactivated SDF-1β/CXCR7-AMPK pathway and increased cleaved caspase-3 expression in EPCs.

Conclusions: Exendin-4 could ameliorate HG-induced EPC dysfunction through regulating the production of IL-6 via SDF-1β/CXCR7-AMPK/p38-MAPK axis.

Keywords: Diabetes mellitus; Endothelial progenitor cell dysfunction; Exendin-4; Interleukin-6; SDF-1β/CXCR7–AMPK/p38-MAPK axis.

PubMed Disclaimer

References

    1. Pippitt K, Li M, Gurgle HE (2016) Diabetes mellitus: screening and diagnosis. Am Fam Physician 93(2):103–109 - PubMed
    1. Lipska KJ, Krumholz H, Soones T, Lee SJ (2016) Polypharmacy in the aging patient: a review of glycemic control in older adults with type 2 diabetes. JAMA 315(10):1034–1045. https://doi.org/10.1001/jama.2016.0299 - DOI - PubMed - PMC
    1. Hinnen D (2017) Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabetes Spectr 30(3):202–210. https://doi.org/10.2337/ds16-0026 - DOI - PubMed - PMC
    1. D'Alessio D (2016) Is GLP-1 a hormone: whether and when? J Diabetes Investig. https://doi.org/10.1111/jdi.12466 - DOI - PubMed - PMC
    1. Cao Y, Gao W, Jusko WJ (2012) Pharmacokinetic/pharmacodynamic modeling of GLP-1 in healthy rats. Pharm Res 29(4):1078–1086. https://doi.org/10.1007/s11095-011-0652-x - DOI - PubMed

MeSH terms

LinkOut - more resources