Background: Studying diabetes and obesity is a priority for Qatar and for the entire world. Fibroblast growth factor 21 (FGF21) is a member of the FGF superfamily that has important endocrine functions in the regulation of glucose metabolism. Elevated plasma levels of FGF21 are seen in humans with type 2 diabetes and mouse models where FGF21-resistance is associated with a reduced response to the blood glucose and insulin sensitizing actions of FGF21. There is, however, a lack of data on the effects of FGF21 on the vasculature. The objective of this study is to determine whether FGF21 and/or the FGFR1 receptor is present in endothelial cells and to determine whether FGF21 protects endothelial cells against hyperglycaemia-induced oxidative stress and uncoupling of eNOS. Methodology: RT-PCR and Western Blot techniques were used to determine the presence of FGF21/FGFR1 mRNA and protein in mouse microvascular endothelial (MMEC) and human umbilical vein endothelial (HUVEC) cell cultures. Endothelial cell cultures were treated with FGF21 to investigate the physiologic role of FGF21 in vascular tissue and to determine whether FGF21 protects the endothelial cell against glucose-induced toxicity. Western blot techniques and the dimeric/monomeric ratio were used to determine eNOS uncoupling. CM-H2DCFDA, an indicator for superoxide, was used to assess oxidative stress. Results: FGFR1 and FGF21 proteins are both expressed in MMECs exposed to high (HG) and normal (NG) glucose levels. FGFR1 levels were not changed in MMECs exposed to HG and treated with FGF21 (p=0.9; N=3) or in NG (p=0.4; N=3). For CM-H2DCFDA staining, FGF21 treated cells showed a decrease in oxidative stress (N=4). However, the eNOS dimer/monomer ratio was not affected by FGF21 in HG or NG (p=0.3; p=0.6 respectively, N=4). In HUVECs, FGFR1 is expressed in cells exposed to HG or NG (p=0.23; N3). FGF21 treatment did not affect the levels of FGFR1 in HG or NG (p=0.99; p=0.8 respectively, N=3). The eNOS dimer/monomer ratio decreased in cells exposed to HG, but was corrected following FGF21 treatment (p=0.1; N=3). Conclusion: FGF21 reduces glucose-induced oxidative stress and may , in addition to its metabolic actions, have an endothelial-vascular protective action. Supported by UREP10-034-3-009.


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