Anti-TCR therapy combined with fingolimod for reversal of diabetic hyperglycemia by β cell regeneration in the LEW.1AR1-iddm rat model of type 1 diabetes

Jörns, Anne; Akin, Muharrem; Arndt, T.; Terbish, Taivankhuu; Vilsendorf, Andreas Meyer zu; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

doi:10.1007/s00109-014-1137-2

Cited by 19 publications

(56 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animals in groups 1 and 4 received 0.9% NaCl solution. Anti-TCR causes slight lymphocyte reduction in the periphery (,20%), which disappears within 1 week after cessation of therapy (25). Anti-TNF-a was without effect and also did not further reduce the lymphocyte count in combination therapy with anti-TCR (data not shown).…”

Section: Experimental Groupsmentioning

confidence: 92%

“…As has been documented in diabetic LEW.1AR1-iddm (IDDM) rats, as well as in pancreases from patients with T1D (3), the islet-infiltrating immune cells produce and release, along with interleukin (IL)-1b, TNF-a as the dominating proinflammatory cytokine (3,5,25).…”

mentioning

confidence: 84%

“…Congenic rats (for details see http://www.mh-hannover .de/3642.html) were bred and maintained as described (25,30). Experimental procedures were approved by the District Government of Hannover (LAVES, nos.…”

Section: Animalsmentioning

confidence: 99%

“…Combination therapies, at variance from monotherapies, have shown promising results in T1D (25)(26)(27)(28)(29) and other autoimmune diseases (11,14,15). We therefore investigated in the IDDM rat, an animal model of human T1D, which mirrors the human T1D situation most closely (3,5,30,31), whether a combination therapy of anti-TNF-a, which suppresses TNF-a release from all immune cells, with anti-T-cell receptor (TCR), which suppresses proinflammatory cytokine release from activated T cells, can be successful.…”

mentioning

confidence: 99%

“…Both antibodies bind noncovalently to the TCR/CD3 complex and modulate T cells by affecting the trans-signaling pathway (32,33). Anti-TCR is used in rats because anti-CD3 is available for mice (33) and humans (33,34) but not for rats (25,35). We show in this study that this combination therapy scheme is capable of successfully reversing the diabetic metabolic state.…”

mentioning

confidence: 99%

See 4 more Smart Citations

TNF-α Antibody Therapy in Combination With the T-Cell–Specific Antibody Anti-TCR Reverses the Diabetic Metabolic State in the LEW.1AR1-iddmRat

et al. 2015

Self Cite

View full text Add to dashboard Cite

Anti–tumor necrosis factor-α (TNF-α) therapy (5 mg/kg body weight), alone or combined with the T-cell–specific antibody anti–T-cell receptor (TCR) (0.5 mg/kg body weight), was performed over 5 days immediately after disease manifestation to reverse the diabetic metabolic state in the LEW.1AR1-iddm rat, an animal model of human type 1 diabetes. Only combination therapy starting at blood glucose concentrations below 15 mmol/L restored normoglycemia and normalized C-peptide. Increased β-cell proliferation and reduced apoptosis led to a restoration of β-cell mass along with an immune cell infiltration–free pancreas 60 days after the end of therapy. This combination of two antibodies, anti-TCR/CD3, as a cornerstone compound in anti–T-cell therapy, and anti–TNF-α, as the most prominent and effective therapeutic antibody in suppressing TNF-α action in many autoimmune diseases, was able to reverse the diabetic metabolic state. With increasing blood glucose concentrations during the disease progression, however, the proapoptotic pressure on the residual β-cell mass increased, ultimately reaching a point where the reservoir of the surviving β-cells was insufficient to allow a restoration of normal β-cell mass through regeneration. The present results may open a therapeutic window for reversal of diabetic hyperglycemia in patients, worthwhile of being tested in clinical trials.

show abstract

Section: Experimental Groupsmentioning

confidence: 92%

mentioning

confidence: 84%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

TNF-α Antibody Therapy in Combination With the T-Cell–Specific Antibody Anti-TCR Reverses the Diabetic Metabolic State in the LEW.1AR1-iddmRat

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

Animal models of human type 1 diabetes for evaluating combination therapies and successful translation to the patient with type 1 diabetes

Lenzen

2017

Diabetes Metabolism Res

Self Cite

View full text Add to dashboard Cite

Animal models of human type 1 diabetes will be of a great importance for the evaluation of new combination therapies with curative potential. However, reliable predictive power for successful translation to patients with type 1 diabetes is crucial. This will be particularly important in the future when evaluating success of new combination therapies that show great promise for preservation and restoration of beta cell mass and thereby reverse the type 1 diabetic hyperglycaemia. But not all spontaneous animal models are equally well suited for this purpose. The advantages and disadvantages of the three spontaneous rat models (BioBreeding diabetes-prone [BB] rat, Komeda [KDP] rat, and LEW.1AR1-iddm [IDDM] rat) as well as the NOD mouse, compared with the characteristics of human type 1 diabetes, are considered in this review.

show abstract

The potential application of Cordyceps in metabolic‐related disorders

Cao

Yang

Zhou

2019

Phytotherapy Research

View full text Add to dashboard Cite

Changes in the global economy resulted in sedentary lifestyle and excessive calorie intake, increasing the incidence of metabolic diseases, which subsequently became a universal public concern. The difficulties of managing chronic diseases did not dampen researchers' enthusiasm for studying new therapeutics or adjuvant treatments. Cordyceps spp. is a kind of traditional Chinese herbal medicine; however, our understanding of this medicine remains at an initial stage. Recently, an increasing number of studies have demonstrated the potential of Cordyceps as a therapeutic agent for the effective treatment of metabolic-related disorders by exerting a variety of activities, including but not limited to anti-inflammatory, immunoregulatory, hypoglycemic, renoprotective and cardiovascular-protective effects. This article reviews the potential efficacy and underlying mechanisms of Cordyceps and its major bioactive ingredients in metabolic syndrome and its associated comorbidities.

show abstract

Anti-TCR therapy combined with fingolimod for reversal of diabetic hyperglycemia by β cell regeneration in the LEW.1AR1-iddm rat model of type 1 diabetes

Cited by 19 publications

References 46 publications

TNF-α Antibody Therapy in Combination With the T-Cell–Specific Antibody Anti-TCR Reverses the Diabetic Metabolic State in the LEW.1AR1-iddmRat

TNF-α Antibody Therapy in Combination With the T-Cell–Specific Antibody Anti-TCR Reverses the Diabetic Metabolic State in the LEW.1AR1-iddmRat

Animal models of human type 1 diabetes for evaluating combination therapies and successful translation to the patient with type 1 diabetes

The potential application of Cordyceps in metabolic‐related disorders

Contact Info

Product

Resources

About