Insulin-mimetic effects of vanadate in preventing the increase of P450IIIA and P450IA subfamily proteins in streptozotocin-diabetic rats.
The insulin-mimetic effects of vanadate in preventing the increase in the level and activity of several P450 proteins in streptozotocin-diabetic rats were examined, in order to extend knowledge of the insulin-like actions of vanadate from glucose metabolism to P450-dependent metabolism. The diabetic state caused by the pancreatic beta cell toxin streptozotocin results, like the diabetes of genetic origin, in major alterations in the expression of P450 isozymes. We focused our attention on the P450III and P450I isoforms, known to be altered during the onset of diabetes. We found an increase in P450IIIA1-linked erythromycin demethylase activity (to about double the control level) and in the relative levels of P450III and P450I isozymes after 2 weeks of uncontrolled diabetes. These parameters were not different from control values in rats given vanadate in drinking water for 2 weeks after streptozotocin administration or in insulin-treated rats. In summary, vanadate appears to exert insulin-mimetic actions on the P450III and P450I family proteins that have a key role in cytochrome P450-dependent metabolism.
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Experimental Liver Toxicology Unit, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Guaitani
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000494:pharmacology*
D007328:Insulin; D014638:Vanadates; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating