Aldose reductase inhibitors and their potential for the treatment of diabetic complications. 1994

D R Tomlinson, and E J Stevens, and L T Diemel
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK.

Aldose reductase converts glucose to sorbitol, which is further processed to fructose. The enzyme is present in most tissues and its possible physiological role is to produce an electrically neutral, non-diffusible osmolyte in cells exposed to hypertonicity, as typified by the renal medullary cells of the loop of Henlé. The enzyme has a low affinity for glucose, and under normal conditions it processes little substrate. However, in diabetes mellitus, the marked rise in intracellular glucose that occurs in some cells causes marked production of sorbitol. The increased flux and accumulation of sorbitol is damaging to cells and may result in some of the long-term complications of diabetes. In this review, David Tomlinson, Elizabeth Stevens and Lara Diemel discuss the role of aldose reductase and the potential of its inhibitors as therapeutic agents targeted at chronic diabetic complications.

UI MeSH Term Description Entries
D003920 Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D003928 Diabetic Nephropathies KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE. Diabetic Glomerulosclerosis,Glomerulosclerosis, Diabetic,Diabetic Kidney Disease,Diabetic Nephropathy,Intracapillary Glomerulosclerosis,Kimmelstiel-Wilson Disease,Kimmelstiel-Wilson Syndrome,Nodular Glomerulosclerosis,Diabetic Kidney Diseases,Glomerulosclerosis, Nodular,Kidney Disease, Diabetic,Kidney Diseases, Diabetic,Kimmelstiel Wilson Disease,Kimmelstiel Wilson Syndrome,Nephropathies, Diabetic,Nephropathy, Diabetic,Syndrome, Kimmelstiel-Wilson
D003929 Diabetic Neuropathies Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325) Diabetic Amyotrophy,Diabetic Autonomic Neuropathy,Diabetic Neuralgia,Diabetic Polyneuropathy,Neuralgia, Diabetic,Asymmetric Diabetic Proximal Motor Neuropathy,Diabetic Asymmetric Polyneuropathy,Diabetic Mononeuropathy,Diabetic Mononeuropathy Simplex,Diabetic Neuropathy, Painful,Mononeuropathy, Diabetic,Symmetric Diabetic Proximal Motor Neuropathy,Amyotrophies, Diabetic,Amyotrophy, Diabetic,Asymmetric Polyneuropathies, Diabetic,Asymmetric Polyneuropathy, Diabetic,Autonomic Neuropathies, Diabetic,Autonomic Neuropathy, Diabetic,Diabetic Amyotrophies,Diabetic Asymmetric Polyneuropathies,Diabetic Autonomic Neuropathies,Diabetic Mononeuropathies,Diabetic Mononeuropathy Simplices,Diabetic Neuralgias,Diabetic Neuropathies, Painful,Diabetic Neuropathy,Diabetic Polyneuropathies,Mononeuropathies, Diabetic,Mononeuropathy Simplex, Diabetic,Mononeuropathy Simplices, Diabetic,Neuralgias, Diabetic,Neuropathies, Diabetic,Neuropathies, Diabetic Autonomic,Neuropathies, Painful Diabetic,Neuropathy, Diabetic,Neuropathy, Diabetic Autonomic,Neuropathy, Painful Diabetic,Painful Diabetic Neuropathies,Painful Diabetic Neuropathy,Polyneuropathies, Diabetic,Polyneuropathies, Diabetic Asymmetric,Polyneuropathy, Diabetic,Polyneuropathy, Diabetic Asymmetric,Simplex, Diabetic Mononeuropathy,Simplices, Diabetic Mononeuropathy
D003930 Diabetic Retinopathy Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION. Diabetic Retinopathies,Retinopathies, Diabetic,Retinopathy, Diabetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000449 Aldehyde Reductase An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. Aldose Reductase,Aldose Reductase Ia,Aldose Reductase Ib,Erythrose Reductase,Xylose Reductase,Reductase Ia, Aldose,Reductase Ib, Aldose,Reductase, Aldehyde,Reductase, Aldose,Reductase, Erythrose,Reductase, Xylose
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D048909 Diabetes Complications Conditions or pathological processes associated with the disease of diabetes mellitus. Due to the impaired control of BLOOD GLUCOSE level in diabetic patients, pathological processes develop in numerous tissues and organs including the EYE, the KIDNEY, the BLOOD VESSELS, and the NERVE TISSUE. Complications of Diabetes Mellitus,Diabetes-Related Complications,Diabetic Complications,Diabetes Complication,Diabetes Mellitus Complication,Diabetes Mellitus Complications,Diabetes Related Complications,Diabetes-Related Complication,Diabetic Complication

Related Publications

D R Tomlinson, and E J Stevens, and L T Diemel
August 1987, The American journal of medicine,
D R Tomlinson, and E J Stevens, and L T Diemel
January 1992, Pharmacology & therapeutics,
D R Tomlinson, and E J Stevens, and L T Diemel
June 1990, Clinical pharmacy,
D R Tomlinson, and E J Stevens, and L T Diemel
December 1999, Expert opinion on investigational drugs,
D R Tomlinson, and E J Stevens, and L T Diemel
October 2007, The Cochrane database of systematic reviews,
D R Tomlinson, and E J Stevens, and L T Diemel
January 2023, Current diabetes reviews,
D R Tomlinson, and E J Stevens, and L T Diemel
July 2021, Archives of pharmacal research,
D R Tomlinson, and E J Stevens, and L T Diemel
October 2006, Current opinion in investigational drugs (London, England : 2000),
D R Tomlinson, and E J Stevens, and L T Diemel
January 2008, Asia Pacific journal of clinical nutrition,
D R Tomlinson, and E J Stevens, and L T Diemel
January 2016, Mini reviews in medicinal chemistry,
Copied contents to your clipboard!