Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats.
Ascorbic acid (AA) metabolism in streptozotocin (STZ)-induced diabetic rats was determined by examining urinary excretion, renal reabsorption, reductive regeneration, and biosynthesis of AA at 3 and 14 days after STZ administration. AA concentrations in the plasma, liver, and kidney of the diabetic rats were significantly lower than those of controls on d 3, and decreased further as the diabetic state continued. Hepatic AA regeneration significantly decreased in the diabetic rats on d 3 in spite of increased gene expressions of AA regenerating enzymes and was further reduced on d 14. Hepatic activity of L-gulono-gamma-lactone oxidase, a terminal enzyme of hepatic AA biosynthesis, also decreased significantly on d 3 and decreased further on d 14. Urinary excretion of AA was significantly increased on d 3, with an increase in urine volume but no change in gene expressions of renal AA transporters (SVCT1 and SVCT2). Urinary excretion of AA was normalized on d 14. The results suggest that impaired hepatic and renal regeneration, as well as increased urinary excretion and impaired hepatic biosynthesis of AA, contributed to the decrease in AA in plasma and tissues of STZ-induced diabetic rats.
Kashiba
Misato
M
National Institute of Health and Nutrition, Tokyo, Japan.
Oka
Jun
J
Ichikawa
Rumi
R
Kasahara
Emiko
E
Inayama
Takayo
T
Kageyama
Asako
A
Kageyama
Haruaki
H
Osaka
Toshimasa
T
Umegaki
Keizo
K
Matsumoto
Akiyo
A
Ishikawa
Takahiro
T
Nishikimi
Morimitsu
M
Inoue
Masayasu
M
Inoue
Shuji
S
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism; D050544:L-Gulonolactone Oxidase; D008099:Liver / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060347:Sodium-Coupled Vitamin C Transporters; D013401:Sugar Alcohol Dehydrogenases / Q000378:metabolism; D027981:Symporters / Q000378:metabolism
D017931:DNA Primers; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D009249:NADP; D010088:Oxidoreductases; D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; C020666:glutathione dehydrogenase (ascorbate); D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid