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Evaluation of the possibility of selective modulation of retinal glucose transporters in diabetic complications: An experimental study
Kanuj Mishra1, Madhu Nath2, Nabanita Halder2, Thirumurthy Velpandian2
1 Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India
2 Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Correspondence Address:
Prof. Thirumurthy Velpandian
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi - 110 029
India
PURPOSE: To identify the possibility of modulating retinal glucose transporters in diabetic conditions to prevent retinal complications of diabetic retinopathy.
MATERIALS AND METHODS: In silico and in vitro binding assays were performed to assess the effect of genistein and positive controls (pioglitazone and estradiol) on nuclear receptor estrogen receptor beta and peroxisome proliferator-activated receptor gamma (PPARγ). In vivo effects of compounds were tested on diabetic rats. Structural and functional analysis of retina was performed at 28th day followed by gene expression analysis of glucose transporters and nuclear receptors. Pioglitazone and genistein levels were analyzed by liquid chromatography with tandem mass spectrometry.
RESULTS: Genistein showed equi-affinity toward PPARγ in in silico experiments contrary to in vitro findings. In multidose study, their therapeutic effects were observed by analyzing the retinal function. Retinal gene expression studies revealed that both test agents significantly up regulated PPARγ, GLUT4, and down regulated GLUT1. Genistein showed significant up regulation of GLUT4 and down regulation of GLUT1 as compared to PGZ which has been well correlated with the Electroretinography (ERG) outcome.
CONCLUSION: This study showed the possibility of selective upregulation of GLUT4 (independent of PPARγ activation) in the retina of diabetic rats using genistein. Selective modulation of retinal glucose transporters as therapeutic target in ocular diabetic complications can be possibly explored.
How to cite this article:
Mishra K, Nath M, Halder N, Velpandian T. Evaluation of the possibility of selective modulation of retinal glucose transporters in diabetic complications: An experimental study.Indian J Pharmacol 2020;52:495-504
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How to cite this URL:
Mishra K, Nath M, Halder N, Velpandian T. Evaluation of the possibility of selective modulation of retinal glucose transporters in diabetic complications: An experimental study. Indian J Pharmacol [serial online] 2020 [cited 2023 Mar 30 ];52:495-504
Available from: https://www.ijp-online.com/article.asp?issn=0253-7613;year=2020;volume=52;issue=6;spage=495;epage=504;aulast=Mishra;type=0 |
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