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Accumulation of sorbitol In certain tissues such as retina, sorbitol dehydrogenase content is low,63 so sorbitol formed from glucose reduction can accumulate.35 This accumulation can change cellular membrane osmotic pressure and triggers osmotic stress.35 This osmotic stress has been thought to be the main underlying mechanism for diabetic retinopathy64, 65 and has also been implicated in diabetic kidney dysfunction or nephropathy.9 It should be noted that even in the same organ, different cell populations may have different levels of sorbitol dehydrogenase;66 hence, the effect of sorbitol on diabetic tissue is differential