Effects of Dexamethasone on Insulin Receptor in Aging
The aim of this study was to examine the effects of dexamethasone (Dex) on functional properties of the rat insulin receptor (IR). Male Mill Hill hooded rats, 3, 6, 12, 18 and 21 months old, were injected with Dex (4 mg/kg) and rat liver and erythrocytes were used for experiments 18 h after Dex administration. Treatment with Dex lowered the specific binding (SB) of insulin (INS) in the liver of 3- and 18-month-old rats and concentration of INS binding sites (N1 N2) and the dissociation constant of low-affinity binding sites (Kd2) in the liver of 6- and 18-month-old rats. In addition, Dex treatment lowered the liver IR protein level in all analyzed groups, except 21-month-old rats where it remained unchanged, but raised the IR mRNA level in 18-month-old rats. In erythrocytes, treatment with Dex decreased SB and Kd2 (in animals 3 and 6 months old) and N] (in ones 3 and 18 months old). Following Dex treatment, the INS plasma level increased (in rats 3,18 and 21 months old), while glucose (Glu) concentration increased in 3 and 12 months old, but decreased in 6- and 21-month-old rats. In summary, Dex exerts the strongest effect on the erythrocyte IR of 3- and 6-month-old rats and the hepatic IR of 18-month-old rats. IR in both tissues is almost insensitive to Dex in 12- and 21-month-old rats. The pattern of age-related changes of IR induced by Dex does not correlate with changes of plasma Glu and INS.
KeywordsDexamethasone insulin receptor aging liver erythrocytes
Unable to display preview. Download preview PDF.
- 16.Koricanac G., Isenovic E., Stojanovic-Susulic V., Miskovic D., Zakula Z., Ribarac-Stepic N. (2006) Time dependent effect of dexamethasone on serum insulin level and insulin receptors in rat liver and erythrocytes. General Physiol. Biophys. 25, 11–24.Google Scholar
- 19.Lowry H. D., Rosenbrough J. N., Farr A. L., Randall J. R. (1951) Protein measurement with Folin phenol reagent. J. Biol. Chem. 153, 265–275.Google Scholar
- 25.Opherk C., Tranche, E, Kellendonk C., Kohlmuller D., Schulze A., Schmid W., Schutz G. (2004) Inactivation of the glucocorticoid receptor in hepatocytes leads to fasting hypoglycemia and ameliorates hyperglycemia in streptozotocin-induced diabetes mellitus. Mol. Endocrinol. 18, 1346–1353.CrossRefGoogle Scholar
- 29.Rutter G. A. (2000) Diabetes: the importance of the liver. Curr. Biol. 10, R736-R738.Google Scholar
- 30.Saad M. J., Folli F., Araki E., Hashimoto N., Csermely P., Kahn C. R. (1994) Regulation of insulin receptor, insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-F442A adipocytes. Effects of differentiation, insulin, and Dexamethasone. Mol. Endocrinol. 8, 545–557.PubMedGoogle Scholar
- 32.Sambrook J., Fritsch E. F., Maniatis T. (1989) In: Nolan C., Ferguson M. (eds) Molecular Cloning: A Laboratory Manual. 2nd edn. Cold Spring Harbour Laboratory Press, New York.Google Scholar
- 33.Sevaljevic L., Isenovic E., Vulovic M., Macvanin M., Zakula Z., Kanazir D., Ribarac-Stepic N. (2001) The responses of rat liver glucocorticoid receptors and genes for tyrosine aminotransferase, alpha-2-macroglobulin and gamma-fibrinogen to adrenalectomy-, dexamethasone- and inflammation-induced changes in the levels of glucocorticoids and proinflammatory cytokines. Biol. Signals Recept. 10, 299–309.CrossRefGoogle Scholar
- 36.Tikhonova N. E., Tatarinova, G. Sh., Pivina S. G., Shaliapina V. G. (1991) Changes in the receptor binding of Dexamethasone and insulin by blood cells in rats after hydrocortisone administration in early postnatal ontogenesis. Probl. Endokrinol. (Mosk.) 37, 47–50.Google Scholar
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.