Myo-inositol and sorbitol metabolism in relation to peripheral nerve function in experimental diabetes in the rat: the effect of aldose reductase inhibition.
A possible relationship between increased sorbitol concentration and decreased myo-inositol concentration in peripheral nerves of diabetic rats has been examined. To this end, sorbinil, an aldose reductase inhibitor, was used either to prevent or reverse elevation of nerve sorbitol concentration in diabetic rats. Sorbinil treatment at 20 mg . kg-1 . day-1 prevented elevation of nerve sorbitol levels in early diabetes and reduced sorbitol concentration from 2.38 to 0.51 mumol/g in rats diabetic for 10 weeks. This treatment reduced the increase in nerve fructose concentration and prevented the reduced myo-inositol concentration found in diabetic rat nerve (control 3.63, diabetic 2.40, diabetic/sorbinil, 3.56 mumol/g). Sorbinil treatment did not prevent a significant slowing of motor-nerve conduction velocity at 10 weeks although treatment reduced the extent of slowing. Sorbinil treatment at 25 mg . kg-1 . day-1 reduced elevated sorbitol and fructose concentrations in diabetic in diabetic rat nerve and normalised myo-inositol concentration. Myo-Inositol treatment at 650 mg . kg-1 . day-1 did not affect the elevated concentrations of sorbitol, fructose or glucose in peripheral nerves of diabetic rats, but it did restore reduced myo-inositol concentration. Both sorbinil and myo-inositol treatment partially reversed the slowing of motor-nerve conduction velocity in diabetic rats. These results are discussed in relation to the involvement of sorbitol and myo-inositol metabolism in the aetiology of diabetic neuropathy.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D010525:Peripheral Nerves / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000503:physiopathology; D013012:Sorbitol / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose