Aldose reductase converts glucose to sorbitol, which is trapped inside cells
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Aldose reductase converts glucose to sorbitol, which sorbitol dehydrogenase then converts to fructose. The pathway is normally minor, but becomes significant when intracellular glucose is high.
Sorbitol is osmotically active and cannot leave the cell, so it accumulates and draws water in.
The affected tissues are precisely those that take up glucose without insulin, so intracellular glucose mirrors blood glucose:
- Lens: osmotic swelling causing cataract
- Schwann cells and peripheral nerve: contributing to neuropathy
- Retina and kidney
- Seminal vesicles, where fructose production is the normal physiological purpose
The pathway also consumes NADPH, depleting reduced glutathione and adding oxidative stress, and the resulting fructose contributes to glycation.
This is one of four proposed mechanisms of diabetic microvascular disease, alongside advanced glycation end products, protein kinase C activation and the hexosamine pathway.
Galactitol accumulates by the same enzyme in galactosaemia, which is why cataracts occur there too.