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Aldose Reductase: a cause and a potential target for the treatment of diabetic complications

Abstract

Diabetes mellitus, a disorder of metabolism, results in the elevation of glucose level in the blood. In this hyperglycaemic condition, aldose reductase overexpresses and leads to further complications of diabetes through the polyol pathway. Glucose metabolism-related disorders are the accumulation of sorbitol, overproduction of NADH and fructose, reduction in NAD+, and excessive NADPH usage, leading to diabetic pathogenesis and its complications such as retinopathy, neuropathy, and nephropathy. Accumulation of sorbitol results in the alteration of osmotic pressure and leads to osmotic stress. The overproduction of NADH causes an increase in reactive oxygen species production which leads to oxidative stress. The overproduction of fructose causes cell death and non-alcoholic fatty liver disease. Apart from these disorders, many other complications have also been discussed in the literature. Therefore, the article overviews the aldose reductase as the causative agent and a potential target for the treatment of diabetic complications. So, aldose reductase inhibitors have gained much importance worldwide right now. Several inhibitors, like derivatives of carboxylic acid, spirohydantoin, phenolic derivatives, etc. could prevent diabetic complications are discussed in this article.

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Acknowledgements

The authors acknowledge the support received from the Central University of Punjab, Bathinda, India, in writing this manuscript. VA and PS are grateful to the CSIR, New Delhi, for the award of the fellowship. We thank Subhasmita Mahapatra for reading the manuscript.

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Thakur, S., Gupta, S.K., Ali, V. et al. Aldose Reductase: a cause and a potential target for the treatment of diabetic complications. Arch. Pharm. Res. 44, 655–667 (2021). https://doi.org/10.1007/s12272-021-01343-5

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Keywords

  • Aldose reductase
  • Aldose reductase inhibitors
  • Diabetic complications
  • Hyperglycaemic conditions
  • Sorbitol dehydrogenase