title: Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats.
abstract: 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.
authors.affiliation: National Institute of Health and Nutrition, Tokyo, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kashiba
authors.forename: Jun
authors.initials: J
authors.lastname: Oka
authors.forename: Rumi
authors.initials: R
authors.lastname: Ichikawa
authors.forename: Emiko
authors.initials: E
authors.lastname: Kasahara
authors.forename: Takayo
authors.initials: T
authors.lastname: Inayama
authors.forename: Asako
authors.initials: A
authors.lastname: Kageyama
authors.forename: Haruaki
authors.initials: H
authors.lastname: Kageyama
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Osaka
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
authors.forename: Akiyo
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Morimitsu
authors.initials: M
authors.lastname: Nishikimi
authors.forename: Masayasu
authors.initials: M
authors.lastname: Inoue
authors.forename: Shuji
authors.initials: S
authors.lastname: Inoue
mesh_terms: 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
chemical_list: 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