Effects of vanadate on hepatic cytochrome P-450 expression in streptozotocin-diabetic rats.
The ability of sodium metavanadate to reverse the effects of streptozotocin-induced diabetes on hepatic cytochrome P-450 isozymes was examined in male rats. Streptozotocin caused P-450h levels to fall 95%, and P-450j and P-450b levels to rise 8- and 40-fold, respectively, after 1 week. When diabetic rats were administered metavanadate in the drinking water for 7 days, P-450h apoprotein and mRNA levels remained no different from those of untreated diabetic rats, whereas levels of P-450b and P-450j decreased toward those of control rats. Metavanadate also lowered serum triglyceride and 3-hydroxybutyrate levels without lowering serum glucose in the diabetic rats. Furthermore, P-450h mRNA levels correlated well with levels of P-450h apoprotein for all treatment groups, indicating that P-450h suppression in diabetic rats is under pretranslational control and is independent of the increased expressions of P-450j and P-450b, and of the hyperlipidemia and ketosis that occurs in diabetes. Vanadate is capable of separating the effects of diabetes on expression of individual P-450 isozymes.
Department of Pharmacology, Emory University, Atlanta, GA 30322.
B S
BS
Donahue
E T
ET
Morgan
D020155:3-Hydroxybutyric Acid; D000510:Alpha-Globulins / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006885:Hydroxybutyrates / Q000097:blood; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000494:pharmacology*
D000510:Alpha-Globulins; D001786:Blood Glucose; D006885:Hydroxybutyrates; D012333:RNA, Messenger; D014280:Triglycerides; C013803:alpha 2u globulin; D014638:Vanadates; D003577:Cytochrome P-450 Enzyme System; D020155:3-Hydroxybutyric Acid