Role in Diabetes
Diabetes mellitus is recognized as a leading cause of new cases of blindness, and is associated with increased risk for painful neuropathy, heart disease and kidney failure. Many theories have been advanced to explain mechanisms leading to diabetic complications, including stimulation of glucose metabolism by the polyol pathway. Additionally, the enzyme is located in the eye (cornea, retina, lens), kidney, and the myelin sheath–tissues that are often involved in diabetic complications. Under normal glycemic conditions, only a small fraction of glucose is metabolized through the polyol pathway, as the majority is phosphorylated by hexokinase, and the resulting product, glucose-6-phosphate, is utilized as a substrate for glycolysis or pentose phosphate metabolism. However, in response to the chronic hyperglycemia found in diabetics, glucose flux through the polyol pathway is significantly increased. Up to 33% of total glucose utilization in some tissues can be through the polyol pathway. Glucose concentrations are often elevated in diabetics and aldose reductase has long been believed to be responsible for diabetic complications involving a number of organs. Many aldose reductase inhibitors have been developed as drug candidates but virtually all have failed although some such as epalrestat are commercially available in several countries. Additional reductase inhibitors such as ranirestat, ponalrestat, rinalrestat, risarestat, sorbinil, and berberine are currently in clinical trials.
Read more about this topic: Aldose Reductase
Famous quotes containing the words role in and/or role:
“Language makes it possible for a child to incorporate his parents’ verbal prohibitions, to make them part of himself....We don’t speak of a conscience yet in the child who is just acquiring language, but we can see very clearly how language plays an indispensable role in the formation of conscience. In fact, the moral achievement of man, the whole complex of factors that go into the organization of conscience is very largely based upon language.”
—Selma H. Fraiberg (20th century)
“The trouble is that the expression ‘material thing’ is functioning already, from the very beginning, simply as a foil for ‘sense-datum’; it is not here given, and is never given, any other role to play, and apart from this consideration it would surely never have occurred to anybody to try to represent as some single kind of things the things which the ordinary man says that he ‘perceives.’”
—J.L. (John Langshaw)