Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Eller, K; Kirsch, A; Wolf, AM; Sopper, S; Tagwerker, A; Stanzl, U; Wolf, D; Patsch, W; Rosenkranz, AR; Eller, P.
Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy.
Diabetes. 2011; 60(11): 2954-2962.
Doi: 10.2337/db11-0358
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- Führende Autor*innen der Med Uni Graz
- Eller Kathrin
- Co-Autor*innen der Med Uni Graz
- Eller Philipp
- Kirsch Alexander
- Rosenkranz Alexander
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- Abstract:
- OBJECTIVE-To assess the potential role of FoxP3-expressing regulatory T cells (Tregs) in reversing obesity-linked insulin resistance and diabetic nephropathy in rodent models and humans. RESEARCH DESIGN AND METHODS-To characterize the role of Tregs in insulin resistance, human visceral adipose tissue was first evaluated for Treg infiltration and second, the db/db mouse model was evaluated. RESULTS-Obese patients with insulin resistance displayed significantly decreased natural Tregs but an increase in adaptive Tregs in their visceral adipose tissue as compared with lean control subjects. To further evaluate the pathogenic role of Tregs in insulin resistance, the db/db mouse model was used. Treg depletion using an anti-CD25 monoclonal antibody enhanced insulin resistance as shown by increased fasting blood glucose levels as well as an impaired insulin sensitivity. Moreover, Treg-depleted db/db mice developed increased signs of diabetic nephropathy, such as albuminuria and glomerular hyperfiltration. This was paralleled by a proinflammatory milieu in both murine visceral adipose tissue and the kidney. Conversely, adoptive transfer of CD4(+)FoxP3(+) Tregs significantly improved insulin sensitivity and diabetic nephropathy. Accordingly, there was increased mRNA expression of FoxP3 as well as less abundant proinflammatory CD8(+)CD69(+) T cells in visceral adipose tissue and kidneys of Treg-treated animals. CONCLUSIONS-Data suggest a potential therapeutic value of Tregs to improve insulin resistance and end organ damage in type 2 diabetes by limiting the proinflammatory milieu. Diabetes 60:2954-2962, 2011
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cytokines - genetics Cytokines - metabolism
- Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - immunology Diabetes Mellitus, Type 2 - metabolism
- Diabetic Nephropathies - immunology Diabetic Nephropathies - physiopathology Diabetic Nephropathies - prevention and control Diabetic Nephropathies - therapy
- Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism
- Gene Expression Regulation -
- Humans -
- Ikaros Transcription Factor - genetics Ikaros Transcription Factor - metabolism
- Insulin Resistance -
- Intra-Abdominal Fat - metabolism Intra-Abdominal Fat - pathology
- Kidney - metabolism Kidney - pathology Kidney - surgery
- Lymphocyte Depletion - adverse effects
- Lymphocyte Transfusion -
- Male -
- Mice -
- Mice, Obese -
- Obesity - immunology Obesity - metabolism Obesity - pathology
- RNA, Messenger - metabolism
- Receptors, Leptin - genetics
- Specific Pathogen-Free Organisms -
- T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - pathology