Aldose-Reductase Inhibitors for Diabetes . . . AND CRON??

[Guest guest]

The " sorbitol trap " appears to produce many/most diabetic

complications. So, this should be of some interest to CR

practitioners, as glycosilation of proteins, etc. is one of the three

top theories on aging. Anyone who can speak to risks here? There

must be some reason these drugs are not in general use in the U.S.

(though they have been available for several decades in Europe, I

understand).

http://www.molvis.org/molvis/v4/a19/

" Aldose reductase (ALR2) is one of the most thoroughly studied of the

aldo-keto reductases due to its putative involvement in the

pathogenesis of diabetic eye disease [5]. ALR2 catalyzes the NADPH-

dependent reduction of glucose to sorbitol, the first step of the

sorbitol pathway (Figure 1). The pathway is completed by sorbitol

dehydrogenase, which catalyzes the NAD+-dependent oxidation of

sorbitol to fructose. A large body of evidence, derived principally

from experimental animal studies, supports the hypothesis that

enhanced metabolism of glucose through the polyol pathway results in

biochemical imbalances associated with diabetic complications.

Chronic hyperglycemia leads to many changes in target tissues of

diabetes including accumulation of excess polyol, alteration in the

relative abundance of oxidized and reduced nicotinamide coenzymes,

changes in the levels of glycolytic intermediates and loss of

myoinositol and glutathione [6]. Since many of these biochemical

alterations appear to be derived from accelerated flux of glucose

through the sorbitol pathway, ALR2 inhibition represents an

attractive strategy for prevention of diabetic complications. The

beneficial effect of aldose reductase inhibitors (ARIs) in preventing

or substantially delaying the onset of diabetic complications in

experimental models provides strong support to this hypothesis.

Moreover, transgenic animal studies have shown that over-expression

of ALR2 confers an increased susceptibility to diabetic cataract [7]

and morphological changes in the retinal vasculature similar to those

observed in human diabetic retinopathy [8]. Examples of ARIs are

shown in Figure 2. "

P.S. what is the trick for adding html tags (italics, bold) to

messages here? My <i> tags don't work.