Cytochrome P450 in livers of diabetic rats: Regulation by growth hormone and insulin

doi:10.1016/0003-9861(89)90324-X

Archives of Biochemistry and Biophysics

Volume 268, Issue 2, 1 February 1989, Pages 567-575

https://doi.org/10.1016/0003-9861(89)90324-X Get rights and content

Abstract

The effects of pituitary and pancreatic hormones on the change in hepatic cytochrome P450s were studied in alloxan- or streptozotocin-induced male rats. In two major sex-specific forms, P450-male and P450_6β-1, the former was decreased in chronic (5 week) diabetes to only less than one-third of controls and the latter was also reduced in early (1 week) diabetes. In contrast, a main phenobarbital-inducible form, P450b, was enhanced 25- to 30-fold in these diabetic rats. 3-Methylcholanthrene-inducible P448H was also elevated 3-fold in alloxan-induced diabetes. These changes in hepatic contents of P450-male, P450-_6β-1, and P450b, which are under the regulation of pituitary growth hormone, associated well with the reported results of time-dependent changes in growth hormone levels in diabetes (G. S. Tannenbaum (1981) Endocrinology108,76–82), suggesting that the change in growth hormone level is a factor responsible for alterations in hepatic cytochrome P450s. Normalizing effects of insulin on these forms were also studied. Treatment of diabetic rats with insulin reversed the decreased amounts of both P450-male protein and mRNA. Insulin also normalized hepatic contents of P450b, P450_6β-1, and P448H. However, the treatment of hypophysectomized rats with insulin had no effect, and treatment of diabetic rats with growth hormone or a suppressing agent of somatostatin, cysteamine, showed trivial effects on P450-male and P450b. These results suggest that insulin does not act directly as a substitute of growth hormone, but exerts its effect indirectly through the normalization of a growth hormone-mediated process(es) in diabetic rats.

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Cytochrome P450 in livers of diabetic rats: Regulation by growth hormone and insulin

Abstract

Biochem. Pharmacol

Biochem. Pharmacol

J. Biol. Chem

Biochem. Biophys. Res. Commun

Arch. Biochem. Biophys

Japan. J. Pharmacol

J. Biol. Chem

J. Biol. Chem

Biochem. Pharmacol

J. Biol. Chem

J. Biol. Chem

J. Biol. Chem

Arch. Biochem. Biophys

J. Biol. Chem

Arch. Biochem. Biophys

J. Biol. Chem

J. Biol. Chem

Comp. Biochem. Physiol. B

J. Biol. Chem

Arch. Biochem. Biophys

Annu. Rev. Biochem

Crit. Rev. Biochem

Xenobiotica

Xenobiotica

J. Pharmacol. Exp. Ther

J. Pharmacol. Exp. Ther

Drug Metab. Dispos

Carcinogenesis