Hyperinsulinaemia causes a preferential increase in hepatic P4501A2 activity.
Article Details
- CitationCopy to clipboard
Barnett CR, Wilson J, Wolf CR, Flatt PR, Ioannides C
Hyperinsulinaemia causes a preferential increase in hepatic P4501A2 activity.
Biochem Pharmacol. 1992 Mar 17;43(6):1255-61. doi: 10.1016/0006-2952(92)90500-i.
- PubMed ID
- 1562279 [ View in PubMed]
- Abstract
Male NEDH (New England Deaconess Hospital) rats were transplanted with a radiation-induced tumour from a donor male rat and were killed 18 days following transplantation. At the time of killing the insulinoma-bearing animals were severely hypoglycaemic but plasma ketone levels were normal. Insulinoma-bearing animals exhibited higher hepatic O-deethylation of ethoxyresorufin and N-demethylation of ethylmorphine activities when compared to control animals. Similarly, hepatic microsomal preparations from insulinoma-bearing rats were more efficient than control animals in converting the promutagen 2-amino-6-methyldipyrido[1,2-a:3',2']imidazole (Glu-P-1) to mutagenic intermediates in the Ames test. Immunoblot analysis employing polyclonal antibodies against the P4501A and P453A families revealed that insulinoma-bearing rats had higher hepatic P4501A2 apoprotein levels. No major differences in P4503A1 apoprotein levels between insulinoma-bearing and control rats were noted. Subcutaneous administration of insulin to male Wistar rats gave rise to a modest increase in ethoxyresorufin O-deethylase activity and in the ability to activate Glu-P-1 to mutagens in the Ames test. Immunoblot analysis revealed an increase in hepatic P4501A2 apoprotein levels following the treatment with insulin. It is concluded that insulinoma-bearing rats display high P4501A2 activity and the hyperinsulinaemia that characterize this condition is responsible for the effect. Moreover, administration of insulin to other strains of rat, such as Wistar, also enhances P4501A2 activity, presumably as a result of hyperinsulinaemia.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Insulin aspart Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin beef Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin degludec Cytochrome P450 1A2 Protein Humans NoInducerDetails Insulin detemir Cytochrome P450 1A2 Protein Humans NoInducerDetails Insulin glargine Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin glulisine Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin human Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin lispro Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin peglispro Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin pork Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Insulin tregopil Cytochrome P450 1A2 Protein Humans UnknownInducerDetails NN344 Cytochrome P450 1A2 Protein Humans UnknownInducerDetails