Activation of PPAR-γ reduces HPA axis activity in diabetic rats by up-regulating PI3K expression

dc.creatorTorres, Rafael Carvalho
dc.creatorMagalhães, Nathalia Santos
dc.creatorSilva, Patrícia M. R. e
dc.creatorMartins, Marco A.
dc.creatorCarvalho, Vinicius F.
dc.date2017-02-15T15:36:04Z
dc.date2017-02-15T15:36:04Z
dc.date2016
dc.date.accessioned2023-09-27T00:02:49Z
dc.date.available2023-09-27T00:02:49Z
dc.identifierTORRES, Rafael Carvalho; et al. Activation of PPAR-γ reduces HPA axis activity in diabetic rats by up-regulating PI3K expression. Experimental and Molecular Pathology, v.101, n.2, p.290-301, Oct. 2016.
dc.identifier0014-4800
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/17825
dc.identifier10.1016/j.yexmp.2016.10.002
dc.identifier1096-0945
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8896882
dc.descriptionIncreased hypothalamus-pituitary-adrenal axis (HPA) activity in diabetes is strongly associated with several morbidities noted in patients with the disease. We previously demonstrated that hyperactivity of HPA axis under diabetic conditions is associated with up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal and down-regulation of glucocorticoid receptors (GR and MR) in pituitary. This study investigates the role of peroxisome proliferator-activated receptor (PPAR)-γ in HPA axis hyperactivity in diabetic rats. Diabetes was induced by intravenous injection of alloxan into fasted rats. The PPAR-γ agonist rosiglitazone and/or PI3K inhibitor wortmannin were administered daily for 18 consecutive days, starting 3days after diabetes induction. Plasma ACTH and corticosterone were evaluated by radioimmunoassay, while intensities of MC2R, proopiomelanocortin (POMC), GR, MR, PI3K p110α and PPAR-γ were assessed using immunohistochemistry. Rosiglitazone treatment inhibited adrenal hypertrophy and hypercorticoidism observed in diabetic rats. Rosiglitazone also significantly reversed the diabetes-induced increase in the MC2R expression in adrenal cortex. We noted that rosiglitazone reduced the number of corticotroph cells and inhibited both anterior pituitary POMC expression and plasma ACTH levels. Furthermore, rosiglitazone treatment was unable to restore the reduced expression of GR and MR in the anterior pituitary of diabetic rats. Rosiglitazone increased the number of PPAR-γ(+) cells and expression of PI3K p110α in both anterior pituitary and adrenal cortex of diabetic rats. In addition, wortmannin blocked the ability of rosiglitazone to restore corticotroph cell numbers, adrenal hypertrophy and plasma corticosterone levels in diabetic rats. In conclusion, our findings revealed that rosiglitazone down-regulates HPA axis hyperactivity in diabetic rats via a mechanism dependent on PI3K activation in pituitary and adrenal glands.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectDiabetes
dc.subjectRatos
dc.subjectPPAR-γ
dc.subjectHPA axis
dc.subjectDiabetes
dc.subjectGlucorticoids
dc.subjectPI3K
dc.subjectrats
dc.titleActivation of PPAR-γ reduces HPA axis activity in diabetic rats by up-regulating PI3K expression
dc.typeArticle


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