Effects of G-6-PD deficiency, experimentally induced or genetically transmitted, on the sorbitol pathway activity. In vitro and in vivo studies.
Aldose reductase catalyzes the NADPH-linked reduction of hexoses to their respective sugar-alcohols, which are involved in the pathogenesis of "sugar-cataracts". In the lenses, the reaction catalyzed by G-6-PD is the source of NADPH supply blocking sugar-alcohol formation and consequently prevents or delays the onset of "sugar-cataracts". We have investigated the effect of G-6-PD deficiency, either experimentally induced or genetically transmitted, on the sorbitol accumulation in whole cells incubated in high glucose media and on the "sugar-cataracts" formation in a galactosemic rat model. We also screened 31 Negro male adults with diabetes mellitus for red cell G-6-PD deficiency. G-6-PD deficiency produced a significant inhibition on sorbitol accumulation in rat lenses and human red cells incubated in 50 mM glucose. In the galactosemic rat model G-6-PD deficiency experimentally induced with acetaminophen delayed the development of cataracts. Finally, two diabetic individuals were G-6-PD deficient and did not show cataracts whereas cataracts were identified in six other diabetic patients.
Vaca
G
G
División de Genética, Subjefatura de Investigación Científica, Unidad de Investigación Biomédica, Centro Médico de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco.
Ramírez
M G
MG
Vargas
M
M
Mendoza
R
R
Chávez-Anaya
E
E
Medina
M D
MD
Alvarez
A
A
Medina
C
C
Sáenz
G
G
Chávez
M
M
D000082:Acetaminophen / Q000494:pharmacology / Q000633:toxicity; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000378:metabolism*; D000818:Animals; D044383:Black People / Q000235:genetics; D002386:Cataract / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002648:Child; D002701:Chloramphenicol / Q000494:pharmacology; D003364:Costa Rica / Q000453:epidemiology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism; D005693:Galactosemias / Q000150:complications / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000378:metabolism*
D000082:Acetaminophen; D003687:Dehydroepiandrosterone; D013012:Sorbitol; D009249:NADP; D002701:Chloramphenicol; D007064:L-Iditol 2-Dehydrogenase; D000449:Aldehyde Reductase; D005954:Glucosephosphate Dehydrogenase