title: Identification of a selective glucocorticoid receptor ligand for the treatment of chronic inflammation in type 2 diabetes mellitus.
abstract: The present study aimed to identify a new selective glucocorticoid receptor (GR) ligand for the treatment of chronic inflammation in type 2 diabetes mellitus. The IN Cell Analyzer 1000 platform was employed to screen for compounds that may promote GR nuclear translocation. A mammalian two-hybrid system and transactivation assay-were used to analyze the selected GR ligands and evaluate their activities for GR transcription and the recruitment of co-activators. A novel selective GR ligand, compound Q40, was identified that was able to promote GR nuclear translocation in a short period of time. It increased the ability of GR to recruit co-activators in a concentration-dependent manner, but had no positive effect on GR transcriptional activity. In conclusion, an increase in the expression levels of gluconeogeneic genes, induced by the transcriptional activation of GR, is the predisposing factor most commonly associated with the side-effects of glucocorticoids. The results suggest that compound Q40 is a ligand of the GR and exerts an agonistic action on the recruitment of co-activators without sugar dysmetabolism-related side-effects. Thus, compound Q40 has the potential to be used as an anti-inflammatory adjuvant therapy with minimal side-effects in patients with type 2 diabetes mellitus.
authors.affiliation: Health Examination Center, The Second People's Hospital of Jinan, Shandong 250001, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Tan
authors.affiliation: Community Health Service, The Second People's Hospital of Jinan, Shandong 250001, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Cardiovascular Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xiangang
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Comprehensive Interventional Therapy, General Hospital of Jinan Military Area Command, Jinan, Shandong 250021, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Reproductive Medicine, Reproductive Hospital Affiliated to Shandong University, Jinan, Shangdong 250021, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yin
keywords: anti-inflammatory therapy; glucocorticoid receptor; selective ligand