June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Dapagliflozin Decrease Fructose-Induced Oxidative Stress Mediated by NADPH Oxidase via a SGLT-2-Dependent Mechanism in the Lens of Type 2 DM Model
Author Affiliations & Notes
  • Ying-Ying Chen
    Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
    National Yang-Ming University, Taipei, Taiwan
  • Tsung-Tien Wu
    Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
    National Yang-Ming University, Taipei, Taiwan
  • Pei-Wen Cheng
    Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • Footnotes
    Commercial Relationships   Ying-Ying Chen, None; Tsung-Tien Wu, None; Pei-Wen Cheng, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3176. doi:
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      Ying-Ying Chen, Tsung-Tien Wu, Pei-Wen Cheng; Dapagliflozin Decrease Fructose-Induced Oxidative Stress Mediated by NADPH Oxidase via a SGLT-2-Dependent Mechanism in the Lens of Type 2 DM Model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3176.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Great deals of studies have demonstrated that chronic hyperglycemia-induced overproduction of reactive oxygen species (ROS) played a central role in the pathogenesis of diabetic cataract. Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated as an adjunct treatment of type 2 diabetes mellitus. The aim of the present study was to determine the effects of the Dapagliflozin in the rat lens epithelial cell on the eyes of fructose-induced diabetes.

Methods : Both the fructose-fed group and the treatment group were fed with 10% fructose for 12 weeks and the treatment group was treated with Dapagliflozin (1.2 mg/day) beginning at week 10 to 12. Besides, serum fasting glucose level of the rats was measured by Clinical Chemistry Analyzer. Immunoblotting analyses were used to quantify protein levels including NADPH oxidase subunits p67-phox, glucose transporter 1 (GLUT1) and glucose transporter 5 (GLUT5) in the rat lens epithelial cell. All data were expressed as the mean ± SEM (n=12 for each group). A one-way analysis of variance (ANOVA) with Scheffe’s post hoc comparison was employed to compare the group differences.

Results : The protein levels in fructose-fed group showed a significant increase in NADPH oxidase subunits p67-phox (7.9 ± 0.1 vs. 7.3 ± 0.3, *P=0.05), GLUT1 (3.4 ± 0.4 vs. 2.3 ± 0.1, *P=0.05) and GLUT5 (4.6 ± 0.5 vs. 0.2 ± 0.06, *P=0.03) after feeding fructose for 12 weeks compared to control group by immunoblotting analyses. However, the protein levels of p67-phox (6.0 ± 0.8 vs.7.9 ± 0.1, *P=0.05), GLUT1 (1.4 ± 0.4 vs. 3.4 ± 0.4, *P=0.05) and GLUT5 (1.2 ± 0.2 vs. 4.6 ± 0.5, *P=0.03) were significantly decreased in Dapagliflozin-treated group compared with fructose-fed groups.

Conclusions : Collectively, fructose increased NADPH oxidase subunits p67-phoxin, GLUT1 and GLUT5 in the rat lens epithelial cell , while treatment with Dapagliflozin reversed the effect in the rat lens epithelial cell of fructose-induced diabetes. These novel findings suggest that the Dapagliflozin may be a potential pharmacological candidate for preventing diabetic cataract.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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