The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia.
This study examined the induction of electroretinogram abnormalities in hyperglycemia and the possible role of increased polyol pathway activity in the development of these changes. Both diabetic hyperglycemia and galactosemia caused the prolongation of peak latencies and in some cases a reduction in the amplitudes of oscillatory potentials on the b-wave. Diabetic hyperglycemia-associated abnormalities were prevented and normalized by insulin or ADN-138, an aldose reductase inhibitor. Galactosemia-induced abnormalities were inhibited by ADN-138, and were reversed either by ADN-138 treatment or by withdrawal of galactose from the diet. Polyol accumulation was prevented by insulin or ADN-138, and the elevated polyol level was reversed by insulin, ADN-138, or withdrawal of galactose in diabetic hyperglycemia and/or galactosemia. These results suggest that the increased polyol pathway activity in the hyperglycemia may be involved in the development of electroretinogram abnormalities similar to those in human diabetes; therefore, ADN-138 could be a useful drug for therapy of retinopathy in the early diabetic stage.
Segawa
M
M
Central Research Laboratories, Kyorin Pharmaceutical Co, Ltd, Tochigi, Japan.
Hirata
Y
Y
Fujimori
S
S
Okada
K
K
D000818:Animals; D002386:Cataract / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004596:Electroretinography; D004376:Galactitol / Q000378:metabolism*; D005693:Galactosemias / Q000503:physiopathology*; D006943:Hyperglycemia / Q000503:physiopathology*; D007294:Inositol / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism*; D013402:Sugar Alcohols / Q000378:metabolism*
D007328:Insulin; D010078:Oxazines; D011758:Pyrroles; D013402:Sugar Alcohols; D004376:Galactitol; D007294:Inositol; D013012:Sorbitol; C054644:ADN 138