Abstract
Most long-term diabetic patients develop microvascular diseases such as retinopathy, nephropathy and neuropathy. Although tight control of blood glucose greatly reduces the incidence of these complications, a significant fraction of diabetic patients with good glycemic control still develop these diseases. Therefore, it is imperative to understand the underlying mechanisms of these diseases such that effective treatment or preventive methods can be developed to augment euglycemic control. In animal studies, there is strong evidence that aldose reductase, the first and rate-limiting enzyme of the polyol pathway that converts glucose to fructose, plays a key role in the pathogenesis of microvascular complications. However, clinical trials of the aldose reductase inhibitors were disappointing and several pharmaceutical companies had abandoned the development of this line of drugs. In this review, the potential pathogenic mechanisms of the polyol pathway are presented, the evidence for the involvement of the polyol pathway in diabetic complications summarized, and the reasons for the unimpressive results of the clinical trials of the aldose inhibitors discussed. It appears that renewed efforts to develop aldose reductase inhibitors for the treatment and prevention of diabetic complications are warranted.
Keywords: aldose reductase, polyol pathway, diabetic complications, microvascular
Current Drug Targets
Title: Aldose Reductase in Diabetic Microvascular Complications
Volume: 6 Issue: 4
Author(s): S. S.M. Chung and S. K. Chung
Affiliation:
Keywords: aldose reductase, polyol pathway, diabetic complications, microvascular
Abstract: Most long-term diabetic patients develop microvascular diseases such as retinopathy, nephropathy and neuropathy. Although tight control of blood glucose greatly reduces the incidence of these complications, a significant fraction of diabetic patients with good glycemic control still develop these diseases. Therefore, it is imperative to understand the underlying mechanisms of these diseases such that effective treatment or preventive methods can be developed to augment euglycemic control. In animal studies, there is strong evidence that aldose reductase, the first and rate-limiting enzyme of the polyol pathway that converts glucose to fructose, plays a key role in the pathogenesis of microvascular complications. However, clinical trials of the aldose reductase inhibitors were disappointing and several pharmaceutical companies had abandoned the development of this line of drugs. In this review, the potential pathogenic mechanisms of the polyol pathway are presented, the evidence for the involvement of the polyol pathway in diabetic complications summarized, and the reasons for the unimpressive results of the clinical trials of the aldose inhibitors discussed. It appears that renewed efforts to develop aldose reductase inhibitors for the treatment and prevention of diabetic complications are warranted.
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Cite this article as:
Chung S.M. S. and Chung K. S., Aldose Reductase in Diabetic Microvascular Complications, Current Drug Targets 2005; 6 (4) . https://dx.doi.org/10.2174/1389450054021891
DOI https://dx.doi.org/10.2174/1389450054021891 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
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