title: Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice.
abstract: OBJECTIVE
  Type 1 diabetes is a multifactorial inflammatory disease that develops as a result of deregulated immune responses, causing progressive autoimmune destruction of insulin-producing beta cells of pancreas. 2-((4-acetoxyphenyl)-2-chloro-N-methyl) ethylammonium chloride, compound A (CpdA), is a selective glucocorticoid receptor (GR) agonist that displays strong anti-inflammatory and immunomodulatory activities. We investigated the therapeutic effectiveness of CpdA in a pharmacological model of type 1 diabetes in mice.
  
  
  METHODS
  The utility of CpdA in diabetes prevention was evaluated in vivo through its prophylactic administration to male C57BL/6 mice that received multiple low doses of streptozotocin for immunoinflammatory diabetes induction. The effect of CpdA on disease development was studied by measuring blood glucose and insulin level, histopathological examination, determination of the nature of infiltrating cells, pro- and anti-inflammatory cytokine production, and signalling pathways.
  
  
  RESULTS
  Prophylactic in vivo therapy with CpdA conferred protection against development of immunoinflammatory diabetes in mice by dampening the M1/Th1/Th17 immune response and switching it towards an anti-inflammatory M2/Th2/Treg profile, thus preserving beta cell function.
  
  
  CONCLUSIONS
  Anti-diabetic properties of CpdA are mediated through modulation of immune cell-mediated pathways, but without triggering adverse events. These findings provide basic information for the therapeutic use of selective GR agonists in the amelioration of islet-directed autoimmunity.
authors.affiliation: Department of Immunology, Institute for Biological Research 'Sinisa Stankovic', University of Belgrade, Belgrade, Serbia.
authors.forename: T
authors.initials: T
authors.lastname: Saksida
authors.forename: M
authors.initials: M
authors.lastname: Vujicic
authors.forename: I
authors.initials: I
authors.lastname: Nikolic
authors.forename: I
authors.initials: I
authors.lastname: Stojanovic
authors.forename: G
authors.initials: G
authors.lastname: Haegeman
authors.forename: S
authors.initials: S
authors.lastname: Stosic-Grujicic
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D013311:Streptozocin / Q000008:administration & dosage; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C104564:2-(4-acetoxyphenyl)-2-chloro-N-methylethylamine; D000085:Acetates; D000903:Antibiotics, Antineoplastic; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; C575863:NR3C1 protein, mouse; D011965:Receptors, Glucocorticoid; D013311:Streptozocin; D014439:Tyramine