Insulin modulates rat liver glucocorticoid receptor.
This investigation used cytosol fraction of rat liver to examine the effects of insulin (INS) on functional properties of glucocorticoid receptor (GR). Male Wistar rats (220-250 g b.wt.) were injected with INS (50 microg/200 g b.wt, i.p.) and 18 h after INS administration used for experiments. INS-stimulated dissociation of G-R complexes was significantly increased by 133% compared to control level. However, INS treatment significantly stimulated stability of GR protein by 138% above control value. Furthermore, results show that INS stimulated activation of formed cytosol [3H] TA-R complexes by 143% in respect to control. [3H]TA-R complexes from INS treated animals could be activated and accumulated at higher rate in cell nuclei of control animals. The physiological relevance of the data was confirmed by INS-related stimulation of Tryptophan oxigenase (TO) activity. It was observed that INS stimulated TO activity while INS injected to adrenalectomized rats, exhibited less effects compared to control. The results indicate that a glucocorticoid hormone (CORT) enhances INS induced stimulation of TO activity, as evidenced by enhanced enzyme activity. Presented data suggest: that INS treatment leads to modifications of the GR protein and the nuclear components and that INS activates the rat liver CORT signaling pathway which mediates, in part, the activity of TO.
Isenovic
Esma R
ER
Department for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, 11000 Belgrade, Serbia and Montenegro. isenovic@yahoo.com
Zakula
Zorica
Z
Koricanac
G
G
Ribarac-Stepic
Nevena
N
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology; D008099:Liver / Q000737:chemistry* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015398:Signal Transduction; D014366:Tryptophan Oxygenase / Q000502:physiology
D005938:Glucocorticoids; D007328:Insulin; D011965:Receptors, Glucocorticoid; D014366:Tryptophan Oxygenase