Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities.
The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the maximal synthetic rate of this substance in the rats. Treatment of diabetic rats with this regime prevented the decrease in activity of granulation tissue prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining the normal properties of collagen. The decreased plasma AA concentration and granulation tissue PRLase activity in diabetes can also be normalized by the aldose reductase inhibitor tolrestat. We conclude that in diabetic animals there is a true deficiency of AA that may be responsible for some of the changes of collagen observed in diabetes. Treatment with AA or an aldose reductase inhibitor may prevent some of the diabetic complications with underlying collagen abnormalities.
McLennan
S
S
Department of Medicine, University of Sydney, NSW, Australia.
Yue
D K
DK
Fisher
E
E
Capogreco
C
C
Heffernan
S
S
Ross
G R
GR
Turtle
J R
JR
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001206:Ascorbic Acid Deficiency / Q000150:complications / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D005260:Female; D006097:Granulation Tissue / Q000201:enzymology; D009281:Naphthalenes / Q000494:pharmacology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D009281:Naphthalenes; C040550:tolrestat; D003094:Collagen; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D011393:Procollagen-Proline Dioxygenase; D001205:Ascorbic Acid