Document Detail

Attenuation of islet-specific T cell responses is associated with C-peptide improvement in autoimmune type 2 diabetes patients.
MedLine Citation:
PMID:  23286943     Owner:  NLM     Status:  MEDLINE    
The clinical efficacy of peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists in cell-mediated autoimmune diseases results from down-regulation of inflammatory cytokines and autoimmune effector cells. T cell islet autoimmunity has been demonstrated to be common in patients with phenotypic type 2 diabetes mellitus (T2DM) and islet-specific T cells (T(+) ) to be correlated positively with more severe beta cell dysfunction. We hypothesized that the beneficial effects of the PPAR-γ agonist, rosiglitazone, therapy in autoimmune T2DM patients is due, in part, to the immunosuppressive properties on the islet-specific T cell responses. Twenty-six phenotypic T2DM patients positive for T cell islet autoimmunity (T(+) ) were identified and randomized to rosiglitazone (n = 12) or glyburide (n = 14). Beta cell function, islet-specific T cell responses, interleukin (IL)-12 and interferon (IFN)-γ responses and islet autoantibodies were followed for 36 months. Patients treated with rosiglitazone demonstrated significant (P < 0·03) down-regulation of islet-specific T cell responses, although no change in response to tetanus, a significant decrease (P < 0·05) in IFN-γ production and significantly (P < 0·001) increased levels of adiponectin compared to glyburide-treated patients. Glucagon-stimulated beta cell function was observed to improve significantly (P < 0·05) in the rosiglitazone-treated T2DM patients coinciding with the down-regulation of the islet-specific T cell responses. In contrast, beta cell function in the glyburide-treated T2DM patients was observed to drop progressively throughout the study. Our results suggest that down-regulation of islet-specific T cell autoimmunity through anti-inflammatory therapy may help to improve beta cell function in autoimmune phenotypic T2DM patients.
B M Brooks-Worrell; J P Palmer
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-03-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  164-70     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
Autoantibodies / blood
Autoimmunity / drug effects
C-Peptide / blood
Cells, Cultured
Diabetes Mellitus, Type 2 / drug therapy*,  immunology
Disease Progression
Follow-Up Studies
Glyburide / administration & dosage,  adverse effects,  pharmacology
Hypoglycemic Agents / administration & dosage*,  adverse effects,  pharmacology
Interferon-gamma / immunology
Interleukin-12 / immunology
Islets of Langerhans / drug effects,  physiology*
Middle Aged
PPAR gamma / agonists*
T-Cell Antigen Receptor Specificity / immunology
T-Lymphocytes / drug effects,  immunology*
Thiazolidinediones / administration & dosage*,  adverse effects,  pharmacology
Grant Support
Reg. No./Substance:
0/Autoantibodies; 0/C-Peptide; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones; 122320-73-4/rosiglitazone; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma; SX6K58TVWC/Glyburide

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