Chronic treatment with glucocorticoids (GCs) induces several side effects including insulin resistance and adipose tissue remodeling. These may be mediated by the glucocorticoid receptor (GR) actions on gene transcription. Here, we aimed to investigate how GLUT4/insulin pathway is affected in subcutaneous (SC) and mesenteric (ME) adipose tissue in a rat model of hypercortisolism.
Male Wistar rats (12 weeks old) were continuously administered during 4 weeks by an osmotic pump with dexamethasone sodium phosphate 0,5 mg/kg/day (DEX) or with NaCl 0,9%. After euthanasia, subcutaneous (inguinal) and visceral (ME) fat pads were excised, weighted and RNA was extracted and analysed (RTq-PCR, Taqman®) for Insr, Irs1, Irs2, Pik3r1*, Pikcg, Akt1, Slc2a4 gene expression. Gene quantification was performed using the comparative delta-delta CT method. Housekeeping controllers were chosen by testing. Statistical analyzes were performed at significance level of 5%.
All genes except those encoding the catalytic part of PI3K (Pikcg; SC p = 0.4078; ME p = 0.3808), IRS1 in SC (p = 0.0694) and IRS2 in ME (p = 0.3058) showed increased expression in the treated group (DEX). The PI3K regulatory subunit (Pik3r*; SC p = 0.0041; ME p < 0.0001) and the genes encoding subsequent proteins in the signaling pathway, AKT (Akt1; SC p = 0.0127; ME p < 0.0001) and GLUT4(Slc2a4; SC p = 0.0374; ME p = 0.0001), remained increased in both fat pads of DEX.
Although overall insulin resistance is a characteristic effect of hypercortisolism, in the representative fat pads of both subcutaneous and visceral adipose tissue, at least at the transcription level, no signs of resistance were evidenced at all. (This study received financial support from FAPESP 2018/16856-5 and 2016/25129-4)