Differential regulation of hepatic cytochrome P450 monooxygenases in streptozotocin-induced diabetic rats.
The present investigation was carried out to study the expression of major cytochrome P450 (CYP) isozymes in streptozotocin-induced diabetes with concomitant insulin therapy. Male Sprague-Dawley rats were randomly assigned to untreated control, streptozotocin-induced diabetic, insulin-treated groups and monitored for 4 weeks. Uncontrolled hyperglycemia in the early phase of diabetes resulted in differential regulation of cytochrome P450 isozymes. CYP1B1, CYP1A2, heme oxygenase (HO)-2 proteins and CYP1A2-dependent 7-ethoxyresorufin O-deethylase (EROD) activity were upregulated in the hepatic microsomes of diabetic rats. Insulin therapy ameliorated EROD activity and the expression of CYP1A2, CYP1B1 and HO-2 proteins. In addition, CYP2B1 and 2E1 proteins were markedly induced in the diabetic group. Insulin therapy resulted in complete amelioration of CYP2E1 whereas CYP2B1 protein was partially ameliorated. By contrast, CYP2C11 protein was decreased over 99% in the diabetic group and was partially ameliorated by insulin therapy. These results demonstrate widespread alterations in the expression of CYP isozymes in diabetic rats that are ameliorated by insulin therapy.
Sindhu
Ram K
RK
UCLA School of Medicine, Charles R. Drew University of Medicine and Science, Division of Nephrology and Hypertension, Department of Internal Medicine, Los Angeles, CA 90059, USA. rksindhu@cdrewu.edu
Koo
Ja-Ryung
JR
Sindhu
Kunal K
KK
Ehdaie
Ashkan
A
Farmand
Farbod
F
Roberts
Christian K
CK
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D004790:Enzyme Induction; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D007328:Insulin / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D007328:Insulin; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2