Effect of hyperinsulinemia and type 2 diabetes-like hyperglycemia on expression of hepatic cytochrome p450 and glutathione s-transferase isoforms in a New Zealand obese-derived mouse backcross population.
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Pass GJ, Becker W, Kluge R, Linnartz K, Plum L, Giesen K, Joost HG
Effect of hyperinsulinemia and type 2 diabetes-like hyperglycemia on expression of hepatic cytochrome p450 and glutathione s-transferase isoforms in a New Zealand obese-derived mouse backcross population.
J Pharmacol Exp Ther. 2002 Aug;302(2):442-50. doi: 10.1124/jpet.102.033553.
- PubMed ID
- 12130701 [ View in PubMed]
- Abstract
In subgroups of a New Zealand obese mouse-derived backcross population with defined aberrations of glucose homeostasis, a comprehensive study of the hepatic expression of cytochrome P450 and glutathione S-transferase was performed. Three patterns of alterations in response to insulin resistance (normoglycemia/hyperinsulinemia) or diabetes (hyperglycemia/hypoinsulinemia) were observed: mRNA levels of Cyp2b9, Cyp3a16, Cyp4a14, and Gstt2 as assessed by Northern- and dot-blot analysis were increased markedly in liver from diabetic mice with no or only a slight increase in insulin resistant mice. Western-blot analysis detected the corresponding changes of the CYP2B and CYP4A proteins. In contrast, expression of Cyp2c22, Cyp2c29, and Cyp2c40 was reduced in diabetic, but normal in insulin resistant mice. These alterations were correlated with changes in serum free fatty acid levels and, therefore, seem to be mediated by the peroxisome proliferator activated receptor-alpha. Furthermore, expression of Cyp1a2, Cyp7b1, Gstm3, and Gstm6 was reduced in both diabetic and insulin resistant mice. Because this third pattern was not correlated with the alterations of serum free fatty acid levels, it seems to reflect an early alteration in the course of the disease, and may be related to the progression of the syndrome from insulin resistance to the type 2-like diabetes.
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